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Journal articles on the topic 'Peroxisomes'
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1
Somborac, Tamara, Güleycan Lutfullahoglu Bal, Kaneez Fatima, Helena Vihinen, Anja Paatero, Eija Jokitalo, Ville O. Paavilainen, and Svetlana Konovalova. "The subset of peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved." PLOS ONE 18, no. 12 (December 1, 2023): e0295047. http://dx.doi.org/10.1371/journal.pone.0295047.
Full textAbstract:
Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, bile acid synthesis and biosynthesis of sterols and ether lipids. Defects in peroxisomes result in severe genetic diseases, such as Zellweger syndrome and neonatal adrenoleukodystrophy. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter the endoplasmic reticulum (ER) in both wild type (WT) and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the ER, peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that some peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes, instead, mitochondria can be involved.
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South, Sarah T., and Stephen J. Gould. "Peroxisome Synthesis in the Absence of Preexisting Peroxisomes." Journal of Cell Biology 144, no. 2 (January 25, 1999): 255–66. http://dx.doi.org/10.1083/jcb.144.2.255.
Full textAbstract:
Zellweger syndrome and related diseases are caused by defective import of peroxisomal matrix proteins. In all previously reported Zellweger syndrome cell lines the defect could be assigned to the matrix protein import pathway since peroxisome membranes were present, and import of integral peroxisomal membrane proteins was normal. However, we report here a Zellweger syndrome patient (PBD061) with an unusual cellular phenotype, an inability to import peroxisomal membrane proteins. We also identified human PEX16, a novel integral peroxisomal membrane protein, and found that PBD061 had inactivating mutations in the PEX16 gene. Previous studies have suggested that peroxisomes arise from preexisting peroxisomes but we find that expression of PEX16 restores the formation of new peroxisomes in PBD061 cells. Peroxisome synthesis and peroxisomal membrane protein import could be detected within 2–3 h of PEX16 injection and was followed by matrix protein import. These results demonstrate that peroxisomes do not necessarily arise from division of preexisting peroxisomes. We propose that peroxisomes may form by either of two pathways: one that involves PEX11-mediated division of preexisting peroxisomes, and another that involves PEX16-mediated formation of peroxisomes in the absence of preexisting peroxisomes.
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Voorn-Brouwer, Tineke, Astrid Kragt, Henk F. Tabak, and Ben Distel. "Peroxisomal membrane proteins are properly targeted to peroxisomes in the absence of COPI- and COPII-mediated vesicular transport." Journal of Cell Science 114, no. 11 (June 1, 2001): 2199–204. http://dx.doi.org/10.1242/jcs.114.11.2199.
Full textAbstract:
The classic model for peroxisome biogenesis states that new peroxisomes arise by the fission of pre-existing ones and that peroxisomal matrix and membrane proteins are recruited directly from the cytosol. Recent studies challenge this model and suggest that some peroxisomal membrane proteins might traffic via the endoplasmic reticulum to peroxisomes. We have studied the trafficking in human fibroblasts of three peroxisomal membrane proteins, Pex2p, Pex3p and Pex16p, all of which have been suggested to transit the endoplasmic reticulum before arriving in peroxisomes. Here, we show that targeting of these peroxisomal membrane proteins is not affected by inhibitors of COPI and COPII that block vesicle transport in the early secretory pathway. Moreover, we have obtained no evidence for the presence of these peroxisomal membrane proteins in compartments other than peroxisomes and demonstrate that COPI and COPII inhibitors do not affect peroxisome morphology or integrity. Together, these data fail to provide any evidence for a role of the endoplasmic reticulum in peroxisome biogenesis.
4
Bascom, Roger A., Honey Chan, and Richard A. Rachubinski. "Peroxisome Biogenesis Occurs in an Unsynchronized Manner in Close Association with the Endoplasmic Reticulum in Temperature-sensitiveYarrowia lipolyticaPex3p Mutants." Molecular Biology of the Cell 14, no. 3 (March 2003): 939–57. http://dx.doi.org/10.1091/mbc.e02-10-0633.
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Pex3p is a peroxisomal integral membrane protein required early in peroxisome biogenesis, and Pex3p-deficient cells lack identifiable peroxisomes. Two temperature-sensitive pex3 mutant strains of the yeast Yarrowia lipolytica were made to investigate the role of Pex3p in the early stages of peroxisome biogenesis. In glucose medium at 16°C, these mutants underwent de novo peroxisome biogenesis and exhibited early matrix protein sequestration into peroxisome-like structures found at the endoplasmic reticulum-rich periphery of cells or sometimes associated with nuclei. The de novo peroxisome biogenesis seemed unsynchronized, with peroxisomes occurring at different stages of development both within cells and between cells. Cells with peripheral nascent peroxisomes and cells with structures morphologically distinct from peroxisomes, such as semi/circular tubular structures that immunostained with antibodies to peroxisomal matrix proteins and to the endoplasmic reticulum-resident protein Kar2p, and that surrounded lipid droplets, were observed during up-regulation of peroxisome biogenesis in cells incubated in oleic acid medium at 16°C. These structures were not detected in wild-type or Pex3p-deficient cells. Their role in peroxisome biogenesis remains unclear. Targeting of peroxisomal matrix proteins to these structures suggests that Pex3p directly or indirectly sequesters components of the peroxisome biogenesis machinery. Such a role is consistent with Pex3p overexpression producing cells with fewer, larger, and clustered peroxisomes.
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Singin, Öznur, Artur Astapenka, Victor Costina, Sandra Kühl, Nina Bonekamp, Oliver Drews, and Markus Islinger. "Analysis of the Mouse Hepatic Peroxisome Proteome—Identification of Novel Protein Constituents Using a Semi-Quantitative SWATH-MS Approach." Cells 13, no. 2 (January 17, 2024): 176. http://dx.doi.org/10.3390/cells13020176.
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Ongoing technical and bioinformatics improvements in mass spectrometry (MS) allow for the identifying and quantifying of the enrichment of increasingly less-abundant proteins in individual fractions. Accordingly, this study reassessed the proteome of mouse liver peroxisomes by the parallel isolation of peroxisomes from a mitochondria- and a microsome-enriched prefraction, combining density-gradient centrifugation with a semi-quantitative SWATH-MS proteomics approach to unveil novel peroxisomal or peroxisome-associated proteins. In total, 1071 proteins were identified using MS and assessed in terms of their distribution in either high-density peroxisomal or low-density gradient fractions, containing the bulk of organelle material. Combining the data from both fractionation approaches allowed for the identification of specific protein profiles characteristic of mitochondria, the ER and peroxisomes. Among the proteins significantly enriched in the peroxisomal cluster were several novel peroxisomal candidates. Five of those were validated by colocalization in peroxisomes, using confocal microscopy. The peroxisomal import of HTATIP2 and PAFAH2, which contain a peroxisome-targeting sequence 1 (PTS1), could be confirmed by overexpression in HepG2 cells. The candidates SAR1B and PDCD6, which are known ER-exit-site proteins, did not directly colocalize with peroxisomes, but resided at ER sites, which frequently surrounded peroxisomes. Hence, both proteins might concentrate at presumably co-purified peroxisome-ER membrane contacts. Intriguingly, the fifth candidate, OCIA domain-containing protein 1, was previously described as decreasing mitochondrial network formation. In this work, we confirmed its peroxisomal localization and further observed a reduction in peroxisome numbers in response to OCIAD1 overexpression. Hence, OCIAD1 appears to be a novel protein, which has an impact on both mitochondrial and peroxisomal maintenance.
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Kim, Jung-Ae. "Peroxisome Metabolism in Cancer." Cells 9, no. 7 (July 14, 2020): 1692. http://dx.doi.org/10.3390/cells9071692.
Full textAbstract:
Peroxisomes are metabolic organelles involved in lipid metabolism and cellular redoxbalance. Peroxisomal function is central to fatty acid oxidation, ether phospholipid synthesis, bile acidsynthesis, and reactive oxygen species homeostasis. Human disorders caused by genetic mutations inperoxisome genes have led to extensive studies on peroxisome biology. Peroxisomal defects are linkedto metabolic dysregulation in diverse human diseases, such as neurodegeneration and age-relateddisorders, revealing the significance of peroxisome metabolism in human health. Cancer is a diseasewith metabolic aberrations. Despite the critical role of peroxisomes in cell metabolism, the functionaleects of peroxisomes in cancer are not as well recognized as those of other metabolic organelles,such as mitochondria. In addition, the significance of peroxisomes in cancer is less appreciated thanit is in degenerative diseases. In this review, I summarize the metabolic pathways in peroxisomesand the dysregulation of peroxisome metabolism in cancer. In addition, I discuss the potential ofinactivating peroxisomes to target cancer metabolism, which may pave the way for more eectivecancer treatment.
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Heyman, J. A., E. Monosov, and S. Subramani. "Role of the PAS1 gene of Pichia pastoris in peroxisome biogenesis." Journal of Cell Biology 127, no. 5 (December 1, 1994): 1259–73. http://dx.doi.org/10.1083/jcb.127.5.1259.
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Several groups have reported the cloning and sequencing of genes involved in the biogenesis of yeast peroxisomes. Yeast strains bearing mutations in these genes are unable to grow on carbon sources whose metabolism requires peroxisomes, and these strains lack morphologically normal peroxisomes. We report the cloning of Pichia pastoris PAS1, the homologue (based on a high level of protein sequence similarity) of the Saccharomyces cerevisiae PAS1. We also describe the creation and characterization of P. pastoris pas1 strains. Electron microscopy on the P. pastoris pas1 cells revealed that they lack morphologically normal peroxisomes, and instead contain membrane-bound structures that appear to be small, mutant peroxisomes, or "peroxisome ghosts." These "ghosts" proliferated in response to induction on peroxisome-requiring carbon sources (oleic acid and methanol), and they were distributed to daughter cells. Biochemical analysis of cell lysates revealed that peroxisomal proteins are induced normally in pas1 cells. Peroxisome ghosts from pas1 cells were purified on sucrose gradients, and biochemical analysis showed that these ghosts, while lacking several peroxisomal proteins, did import varying amounts of several other peroxisomal proteins. The existence of detectable peroxisome ghosts in P. pastoris pas1 cells, and their ability to import some proteins, stands in contrast with the results reported by Erdmann et al. (1991) for the S. cerevisiae pas1 mutant, in which they were unable to detect peroxisome-like structures. We discuss the role of PAS1 in peroxisome biogenesis in light of the new information regarding peroxisome ghosts in pas1 cells.
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Hoepfner, Dominic, Marlene van den Berg, Peter Philippsen, Henk F. Tabak, and Ewald H. Hettema. "A role for Vps1p, actin, and the Myo2p motor in peroxisome abundance and inheritance in Saccharomyces cerevisiae." Journal of Cell Biology 155, no. 6 (December 3, 2001): 979–90. http://dx.doi.org/10.1083/jcb.200107028.
Full textAbstract:
In vivo time-lapse microscopy reveals that the number of peroxisomes in Saccharomyces cerevisiae cells is fairly constant and that a subset of the organelles are targeted and segregated to the bud in a highly ordered, vectorial process. The dynamin-like protein Vps1p controls the number of peroxisomes, since in a vps1Δ mutant only one or two giant peroxisomes remain. Analogous to the function of other dynamin-related proteins, Vps1p may be involved in a membrane fission event that is required for the regulation of peroxisome abundance. We found that efficient segregation of peroxisomes from mother to bud is dependent on the actin cytoskeleton, and active movement of peroxisomes along actin filaments is driven by the class V myosin motor protein, Myo2p: (a) peroxisomal dynamics always paralleled the polarity of the actin cytoskeleton, (b) double labeling of peroxisomes and actin cables revealed a close association between both, (c) depolymerization of the actin cytoskeleton abolished all peroxisomal movements, and (d) in cells containing thermosensitive alleles of MYO2, all peroxisome movement immediately stopped at the nonpermissive temperature. In addition, time-lapse videos showing peroxisome movement in wild-type and vps1Δ cells suggest the existence of various levels of control involved in the partitioning of peroxisomes.
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Fagarasanu, Monica, Andrei Fagarasanu, Yuen Yi C. Tam, John D. Aitchison, and Richard A. Rachubinski. "Inp1p is a peroxisomal membrane protein required for peroxisome inheritance in Saccharomyces cerevisiae." Journal of Cell Biology 169, no. 5 (May 31, 2005): 765–75. http://dx.doi.org/10.1083/jcb.200503083.
Full textAbstract:
Cells have evolved molecular mechanisms for the efficient transmission of organelles during cell division. Little is known about how peroxisomes are inherited. Inp1p is a peripheral membrane protein of peroxisomes of Saccharomyces cerevisiae that affects both the morphology of peroxisomes and their partitioning during cell division. In vivo 4-dimensional video microscopy showed an inability of mother cells to retain a subset of peroxisomes in dividing cells lacking the INP1 gene, whereas cells overexpressing INP1 exhibited immobilized peroxisomes that failed to be partitioned to the bud. Overproduced Inp1p localized to both peroxisomes and the cell cortex, supporting an interaction of Inp1p with specific structures lining the cell periphery. The levels of Inp1p vary with the cell cycle. Inp1p binds Pex25p, Pex30p, and Vps1p, which have been implicated in controlling peroxisome division. Our findings are consistent with Inp1p acting as a factor that retains peroxisomes in cells and controls peroxisome division. Inp1p is the first peroxisomal protein directly implicated in peroxisome inheritance.
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Kim, Peter K., Robert T. Mullen, Uwe Schumann, and Jennifer Lippincott-Schwartz. "The origin and maintenance of mammalian peroxisomes involves a de novo PEX16-dependent pathway from the ER." Journal of Cell Biology 173, no. 4 (May 22, 2006): 521–32. http://dx.doi.org/10.1083/jcb.200601036.
Full textAbstract:
Peroxisomes are ubiquitous organelles that proliferate under different physiological conditions and can form de novo in cells that lack them. The endoplasmic reticulum (ER) has been shown to be the source of peroxisomes in yeast and plant cells. It remains unclear, however, whether the ER has a similar role in mammalian cells and whether peroxisome division or outgrowth from the ER maintains peroxisomes in growing cells. We use a new in cellula pulse-chase imaging protocol with photoactivatable GFP to investigate the mechanism underlying the biogenesis of mammalian peroxisomes. We provide direct evidence that peroxisomes can arise de novo from the ER in both normal and peroxisome-less mutant cells. We further show that PEX16 regulates this process by being cotranslationally inserted into the ER and serving to recruit other peroxisomal membrane proteins to membranes. Finally, we demonstrate that the increase in peroxisome number in growing wild-type cells results primarily from new peroxisomes derived from the ER rather than by division of preexisting peroxisomes.
11
Rapp, S., R. Saffrich, M. Anton, U. Jakle, W. Ansorge, K. Gorgas, and W. W. Just. "Microtubule-based peroxisome movement." Journal of Cell Science 109, no. 4 (April 1, 1996): 837–49. http://dx.doi.org/10.1242/jcs.109.4.837.
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The association of peroxisomes with cytoskeletal structures was investigated both by electron microscopy and by kinetic analysis of peroxisome movement. The morphological studies indicated distinct interactions of peroxisomes with microtubules and frequently revealed multiple contact sites. The kinetic approach utilised microinjection and import of fluorescein-labeled luciferase in order to mark and track peroxisomes in vivo. Peroxisomal motility was analysed by time-lapse imaging and fluorescence microscopy. According to their movement peroxisomes were classified into two groups. Group 1 peroxisomes comprising the majority of organelles at 37 degrees C moved slowly with an average velocity of 0.024 +/- 0.012 micron/second whereas the movement of group 2 peroxisomes, 10–15% of the total population, was saltatory exhibiting an average velocity of 0.26 +/- 0.17 micron/second with maximal values of more than 2 microns/second. Saltations were completely abolished by the microtubule-depolymerising drug nocodazole and were slightly reduced by about 25% by cytochalasin D which disrupts the actin microfilament system. Double fluorescence labeling of both peroxisomes and microtubules revealed peroxisome saltations linked to distinct microtubule tracks. Cellular depletion of endogenous levels of NTPs as well as the use of 5′-adenylylimidodiphosphate, a nonhydrolysable ATP analog, applied to a permeabilised cell preparation both completely blocked peroxisomal movement. These data suggest an ATPase dependent, microtubule-based mechanism of peroxisome movement. Both the intact and the permeabilised cell system presented in this paper for the first time allow kinetic measurements on peroxisomal motility and thus will be extremely helpful in the biochemical characterisation of the motor proteins involved.
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Geuze, Hans J., Jean Luc Murk, An K. Stroobants, Janice M. Griffith, Monique J. Kleijmeer, Abraham J. Koster, Arie J. Verkleij, Ben Distel, and Henk F. Tabak. "Involvement of the Endoplasmic Reticulum in Peroxisome Formation." Molecular Biology of the Cell 14, no. 7 (July 2003): 2900–2907. http://dx.doi.org/10.1091/mbc.e02-11-0734.
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The traditional view holds that peroxisomes are autonomous organelles multiplying by growth and division. More recently, new observations have challenged this concept. Herein, we present evidence supporting the involvement of the endoplasmic reticulum (ER) in peroxisome formation by electron microscopy, immunocytochemistry and three-dimensional image reconstruction of peroxisomes and associated compartments in mouse dendritic cells. We found the peroxisomal membrane protein Pex13p and the ATP-binding cassette transporter protein PMP70 present in specialized subdomains of the ER that were continuous with a peroxisomal reticulum from which mature peroxisomes arose. The matrix proteins catalase and thiolase were only detectable in the reticula and peroxisomes. Our results suggest the existence of a maturation pathway from the ER to peroxisomes and implicate the ER as a major source from which the peroxisomal membrane is derived.
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Tam, Yuen Yi C., Juan C. Torres-Guzman, Franco J. Vizeacoumar, Jennifer J. Smith, Marcello Marelli, John D. Aitchison, and Richard A. Rachubinski. "Pex11-related Proteins in Peroxisome Dynamics: A Role for the Novel Peroxin Pex27p in Controlling Peroxisome Size and Number in Saccharomyces cerevisiae." Molecular Biology of the Cell 14, no. 10 (October 2003): 4089–102. http://dx.doi.org/10.1091/mbc.e03-03-0150.
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Transcriptome profiling identified the gene PEX25 encoding Pex25p, a peroxisomal membrane peroxin required for the regulation of peroxisome size and maintenance in Saccharomyces cerevisiae. Pex25p is related to a protein of unknown function encoded by the open reading frame, YOR193w, of the S. cerevisiae genome. Yor193p is a peripheral peroxisomal membrane protein that exhibits high sequence similarity not only to Pex25p but also to the peroxisomal membrane peroxin Pex11p. Unlike Pex25p and Pex11p, Yor193p is constitutively expressed in wild-type cells grown in oleic acid-containing medium, the metabolism of which requires intact peroxisomes. Cells deleted for the YOR193w gene show a few enlarged peroxisomes. Peroxisomes are greatly enlarged in cells harboring double deletions of the YOR193w and PEX25 genes, the YOR193w and PEX11 genes, and the PEX25 and PEX11 genes. Yeast two-hybrid analyses showed that Yor193p interacts with Pex25p and itself, Pex25p interacts with Yor193p and itself, and Pex11p interacts only with itself. Overexpression of YOR193w, PEX25, or PEX11 led to peroxisome proliferation and the formation of small peroxisomes. Our data suggest a role for Yor193p, renamed Pex27p, in controlling peroxisome size and number in S. cerevisiae.
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Chang, Jinlan, Andrei Fagarasanu, and Richard A. Rachubinski. "Peroxisomal Peripheral Membrane Protein YlInp1p Is Required for Peroxisome Inheritance and Influences the Dimorphic Transition in the Yeast Yarrowia lipolytica." Eukaryotic Cell 6, no. 9 (July 20, 2007): 1528–37. http://dx.doi.org/10.1128/ec.00185-07.
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ABSTRACT Eukaryotic cells have evolved molecular mechanisms to ensure the faithful inheritance of organelles by daughter cells in order to maintain the benefits afforded by the compartmentalization of biochemical functions. Little is known about the inheritance of peroxisomes, organelles of lipid metabolism. We have analyzed peroxisome dynamics and inheritance in the dimorphic yeast Yarrowia lipolytica. Most peroxisomes are anchored at the periphery of cells of Y. lipolytica. In vivo video microscopy showed that at cell division, approximately half of the anchored peroxisomes in the mother cell are dislodged individually from their static positions and transported to the bud. Peroxisome motility is dependent on the actin cytoskeleton. YlInp1p is a peripheral peroxisomal membrane protein that affects the partitioning of peroxisomes between mother cell and bud in Y. lipolytica. In cells lacking YlInp1p, most peroxisomes were transferred to the bud, with only a few remaining in the mother cell, while in cells overexpressing YlInp1p, peroxisomes were preferentially retained in the mother cell, resulting in buds nearly devoid of peroxisomes. Our results are consistent with a role for YlInp1p in anchoring peroxisomes in cells. YlInp1p has a role in the dimorphic transition in Y. lipolytica, as cells lacking the YlINP1 gene more readily convert from the yeast to the mycelial form in oleic acid-containing medium, the metabolism of which requires peroxisomal activity, than does the wild-type strain. This study reports the first analysis of organelle inheritance in a true dimorphic yeast and identifies the first protein required for peroxisome inheritance in Y. lipolytica.
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Dodt, G., and S. J. Gould. "Multiple PEX genes are required for proper subcellular distribution and stability of Pex5p, the PTS1 receptor: evidence that PTS1 protein import is mediated by a cycling receptor." Journal of Cell Biology 135, no. 6 (December 15, 1996): 1763–74. http://dx.doi.org/10.1083/jcb.135.6.1763.
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PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at least 15 peroxins required for peroxisome biogenesis. Pex5p has a bimodal distribution within the cell, mostly cytosolic with a small amount bound to peroxisomes. This distribution indicates that Pex5p may function as a cycling receptor, a mode of action likely to require interaction with additional peroxins. Loss of peroxins required for protein translocation into the peroxisome (PEX2 or PEX12) resulted in accumulation of Pex5p at docking sites on the peroxisome surface. Pex5p also accumulated on peroxisomes in normal cells under conditions which inhibit protein translocation into peroxisomes (low temperature or ATP depletion), returned to the cytoplasm when translocation was restored, and reaccumulated on peroxisomes when translocation was again inhibited. Translocation inhibiting conditions did not result in Pex5p redistribution in cells that lack detectable peroxisomes. Thus, it appears that Pex5p can cycle repeatedly between the cytoplasm and peroxisome. Altered activity of the peroxin defective in CG7 cells leads to accumulation of Pex5p within the peroxisome, indicating that Pex5p may actually enter the peroxisome lumen at one point in its cycle. In addition, we found that the PTS1 receptor was extremely unstable in the peroxin-deficient CG1, CG4, and CG8 cells. Altered distribution or stability of the PTS1 receptor in all cells with a defect in PTS1 protein import implies that the genes mutated in these cell lines encode proteins with a direct role in peroxisomal protein import.
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Baker, Alison, David J. Carrier, Theresia Schaedler, Hans R. Waterham, Carlo W. van Roermund, and Frederica L. Theodoulou. "Peroxisomal ABC transporters: functions and mechanism." Biochemical Society Transactions 43, no. 5 (October 1, 2015): 959–65. http://dx.doi.org/10.1042/bst20150127.
Full textAbstract:
Peroxisomes are arguably the most biochemically versatile of all eukaryotic organelles. Their metabolic functions vary between different organisms, between different tissue types of the same organism and even between different developmental stages or in response to changed environmental conditions. New functions for peroxisomes are still being discovered and their importance is underscored by the severe phenotypes that can arise as a result of peroxisome dysfunction. The β-oxidation pathway is central to peroxisomal metabolism, but the substrates processed are very diverse, reflecting the diversity of peroxisomes across species. Substrates for β-oxidation enter peroxisomes via ATP-binding cassette (ABC) transporters of subfamily D; (ABCD) and are activated by specific acyl CoA synthetases for further metabolism. Humans have three peroxisomal ABCD family members, which are half transporters that homodimerize and have distinct but partially overlapping substrate specificity; Saccharomyces cerevisiae has two half transporters that heterodimerize and plants have a single peroxisomal ABC transporter that is a fused heterodimer and which appears to be the single entry point into peroxisomes for a very wide variety of β-oxidation substrates. Our studies suggest that the Arabidopsis peroxisomal ABC transporter AtABCD1 accepts acyl CoA substrates, cleaves them before or during transport followed by reactivation by peroxisomal synthetases. We propose that this is a general mechanism to provide specificity to this class of transporters and by which amphipathic compounds are moved across peroxisome membranes.
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Schrader, M., S. J. King, T. A. Stroh, and T. A. Schroer. "Real time imaging reveals a peroxisomal reticulum in living cells." Journal of Cell Science 113, no. 20 (October 15, 2000): 3663–71. http://dx.doi.org/10.1242/jcs.113.20.3663.
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We have directly imaged the dynamic behavior of a variety of morphologically different peroxisomal structures in HepG2 and COS-7 cells transfected with a construct encoding GFP bearing the C-terminal peroxisomal targeting signal 1. Real time imaging revealed that moving peroxisomes interacted with each other and were engaged in transient contacts, and at higher magnification, tubular peroxisomes appeared to form a peroxisomal reticulum. Local remodeling of these structures could be observed involving the formation and detachment of tubular processes that interconnected adjacent organelles. Inhibition of cytoplasmic dynein based motility by overexpression of the dynactin subunit, dynamitin (p50), inhibited the movement of peroxisomes in vivo and interfered with the reestablishment of a uniform distribution of peroxisomes after recovery from nocodazole treatment. Isolated peroxisomes moved in vitro along microtubules in the presence of a microtubule motor fraction. Our data reveal that peroxisomal behavior in vivo is significantly more dynamic and interactive than previously thought and suggest a role for the dynein/dynactin motor in peroxisome motility.
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Galiani, Silvia, Dominic Waithe, Katharina Reglinski, Luis Daniel Cruz-Zaragoza, Esther Garcia, Mathias P. Clausen, Wolfgang Schliebs, Ralf Erdmann, and Christian Eggeling. "Super-resolution Microscopy Reveals Compartmentalization of Peroxisomal Membrane Proteins." Journal of Biological Chemistry 291, no. 33 (June 16, 2016): 16948–62. http://dx.doi.org/10.1074/jbc.m116.734038.
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Membrane-associated events during peroxisomal protein import processes play an essential role in peroxisome functionality. Many details of these processes are not known due to missing spatial resolution of technologies capable of investigating peroxisomes directly in the cell. Here, we present the use of super-resolution optical stimulated emission depletion microscopy to investigate with sub-60-nm resolution the heterogeneous spatial organization of the peroxisomal proteins PEX5, PEX14, and PEX11 around actively importing peroxisomes, showing distinct differences between these peroxins. Moreover, imported protein sterol carrier protein 2 (SCP2) occupies only a subregion of larger peroxisomes, highlighting the heterogeneous distribution of proteins even within the peroxisome. Finally, our data reveal subpopulations of peroxisomes showing only weak colocalization between PEX14 and PEX5 or PEX11 but at the same time a clear compartmentalized organization. This compartmentalization, which was less evident in cases of strong colocalization, indicates dynamic protein reorganization linked to changes occurring in the peroxisomes. Through the use of multicolor stimulated emission depletion microscopy, we have been able to characterize peroxisomes and their constituents to a yet unseen level of detail while maintaining a highly statistical approach, paving the way for equally complex biological studies in the future.
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Zhang, J. W., C. Luckey, and P. B. Lazarow. "Three peroxisome protein packaging pathways suggested by selective permeabilization of yeast mutants defective in peroxisome biogenesis." Molecular Biology of the Cell 4, no. 12 (December 1993): 1351–59. http://dx.doi.org/10.1091/mbc.4.12.1351.
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We have identified five complementation groups of peroxisome biogenesis (peb) mutants in Saccharomyces cerevisiae by a positive selection procedure. Three of these contained morphologically recognizable peroxisomes, and two appeared to lack the organelle altogether. The packaging of peroxisomal proteins in these mutants has been analyzed with a new gentle cell fractionation procedure. It employs digitonin titration for the selective permeabilization of yeast plasma and intracellular membranes. Proteins were measured by enzymatic assay or by quantitative chemiluminescent immunoblotting. With this gentle fractionation method, it was demonstrated that two mutants are selectively defective in assembling proteins into peroxisomes. Peb1-1 packages catalase and acyl-CoA oxidase within peroxisomes but not thiolase. Peb5-1 packages thiolase and acyl-CoA oxidase within peroxisomes but not catalase. The data suggest that the peroxisome biogenesis machinery contains components that are specific for each of three classes of peroxisomal proteins, represented by catalase, thiolase, and acyl-CoA oxidase. In the two mutants lacking morphologically recognizable peroxisomes, peb2-1 and peb4-1, all three enzymes were mislocalized to the cytosol.
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Kim, Jinoh, and Hua Bai. "Peroxisomal Stress Response and Inter-Organelle Communication in Cellular Homeostasis and Aging." Antioxidants 11, no. 2 (January 19, 2022): 192. http://dx.doi.org/10.3390/antiox11020192.
Full textAbstract:
Peroxisomes are key regulators of cellular and metabolic homeostasis. These organelles play important roles in redox metabolism, the oxidation of very-long-chain fatty acids (VLCFAs), and the biosynthesis of ether phospholipids. Given the essential role of peroxisomes in cellular homeostasis, peroxisomal dysfunction has been linked to various pathological conditions, tissue functional decline, and aging. In the past few decades, a variety of cellular signaling and metabolic changes have been reported to be associated with defective peroxisomes, suggesting that many cellular processes and functions depend on peroxisomes. Peroxisomes communicate with other subcellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum (ER), and lysosomes. These inter-organelle communications are highly linked to the key mechanisms by which cells surveil defective peroxisomes and mount adaptive responses to protect them from damages. In this review, we highlight the major cellular changes that accompany peroxisomal dysfunction and peroxisomal inter-organelle communication through membrane contact sites, metabolic signaling, and retrograde signaling. We also discuss the age-related decline of peroxisomal protein import and its role in animal aging and age-related diseases. Unlike other organelle stress response pathways, such as the unfolded protein response (UPR) in the ER and mitochondria, the cellular signaling pathways that mediate stress responses to malfunctioning peroxisomes have not been systematically studied and investigated. Here, we coin these signaling pathways as “peroxisomal stress response pathways”. Understanding peroxisomal stress response pathways and how peroxisomes communicate with other organelles are important and emerging areas of peroxisome research.
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Marelli, Marcello, Jennifer J. Smith, Sunhee Jung, Eugene Yi, Alexey I. Nesvizhskii, Rowan H. Christmas, Ramsey A. Saleem, et al. "Quantitative mass spectrometry reveals a role for the GTPase Rho1p in actin organization on the peroxisome membrane." Journal of Cell Biology 167, no. 6 (December 13, 2004): 1099–112. http://dx.doi.org/10.1083/jcb.200404119.
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We have combined classical subcellular fractionation with large-scale quantitative mass spectrometry to identify proteins that enrich specifically with peroxisomes of Saccharomyces cerevisiae. In two complementary experiments, isotope-coded affinity tags and tandem mass spectrometry were used to quantify the relative enrichment of proteins during the purification of peroxisomes. Mathematical modeling of the data from 306 quantified proteins led to a prioritized list of 70 candidates whose enrichment scores indicated a high likelihood of them being peroxisomal. Among these proteins, eight novel peroxisome-associated proteins were identified. The top novel peroxisomal candidate was the small GTPase Rho1p. Although Rho1p has been shown to be tethered to membranes of the secretory pathway, we show that it is specifically recruited to peroxisomes upon their induction in a process dependent on its interaction with the peroxisome membrane protein Pex25p. Rho1p regulates the assembly state of actin on the peroxisome membrane, thereby controlling peroxisome membrane dynamics and biogenesis.
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Zhang, J. W., Y. Han, and P. B. Lazarow. "Novel peroxisome clustering mutants and peroxisome biogenesis mutants of Saccharomyces cerevisiae." Journal of Cell Biology 123, no. 5 (December 1, 1993): 1133–47. http://dx.doi.org/10.1083/jcb.123.5.1133.
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The goal of this research is to identify and characterize the protein machinery that functions in the intracellular translocation and assembly of peroxisomal proteins in Saccharomyces cerevisiae. Several genes encoding proteins that are essential for this process have been identified previously by Kunau and collaborators, but the mutant collection was incomplete. We have devised a positive selection procedure that identifies new mutants lacking peroxisomes or peroxisomal function. Immunofluorescence procedures for yeast were simplified so that these mutants could be rapidly and efficiently screened for those in which peroxisome biogenesis is impaired. With these tools, we have identified four complementation groups of peroxisome biogenesis mutants, and one group that appears to express reduced amounts of peroxisomal proteins. Two of our mutants lack recognizable peroxisomes, although they might contain peroxisomal membrane ghosts like those found in Zellweger syndrome. Two are selectively defective in packaging peroxisomal proteins and moreover show striking intracellular clustering of the peroxisomes. The distribution of mutants among complementation groups implies that the collection of peroxisome biogenesis mutants is still incomplete. With the procedures described, it should prove straightforward to isolate mutants from additional complementation groups.
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Wang, Shan, HaoXuan Yang, YongLun Fu, XiaoMing Teng, ChiChiu Wang, and WenMing Xu. "The Key Role of Peroxisomes in Follicular Growth, Oocyte Maturation, Ovulation, and Steroid Biosynthesis." Oxidative Medicine and Cellular Longevity 2022 (February 3, 2022): 1–17. http://dx.doi.org/10.1155/2022/7982344.
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The absence of peroxisomes can cause disease in the human reproductive system, including the ovaries. The available peroxisomal gene-knockout female mouse models, which exhibit pathological changes in the ovary and reduced fertility, are listed in this review. Our review article provides the first systematic presentation of peroxisomal regulation and its possible functions in the ovary. Our immunofluorescence results reveal that peroxisomes are present in all cell types in the ovary; however, peroxisomes exhibit different numerical abundances and strong heterogeneity in their protein composition among distinct ovarian cell types. The peroxisomal compartment is strongly altered during follicular development and during oocyte maturation, which suggests that peroxisomes play protective roles in oocytes against oxidative stress and lipotoxicity during ovulation and in the survival of oocytes before conception. In addition, the peroxisomal compartment is involved in steroid synthesis, and peroxisomal dysfunction leads to disorder in the sexual hormone production process. However, an understanding of the cellular and molecular mechanisms underlying these physiological and pathological processes is lacking. To date, no effective treatment for peroxisome-related disease has been developed, and only supportive methods are available. Thus, further investigation is needed to resolve peroxisome deficiency in the ovary and eventually promote female fertility.
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Verner, Zdeněk, Vojtěch Žárský, Tien Le, Ravi Kumar Narayanasamy, Petr Rada, Daniel Rozbeský, Abhijith Makki, et al. "Anaerobic peroxisomes in Entamoeba histolytica metabolize myo-inositol." PLOS Pathogens 17, no. 11 (November 15, 2021): e1010041. http://dx.doi.org/10.1371/journal.ppat.1010041.
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Entamoeba histolytica is believed to be devoid of peroxisomes, like most anaerobic protists. In this work, we provided the first evidence that peroxisomes are present in E. histolytica, although only seven proteins responsible for peroxisome biogenesis (peroxins) were identified (Pex1, Pex6, Pex5, Pex11, Pex14, Pex16, and Pex19). Targeting matrix proteins to peroxisomes is reduced to the PTS1-dependent pathway mediated via the soluble Pex5 receptor, while the PTS2 receptor Pex7 is absent. Immunofluorescence microscopy showed that peroxisomal markers (Pex5, Pex14, Pex16, Pex19) are present in vesicles distinct from mitosomes, the endoplasmic reticulum, and the endosome/phagosome system, except Pex11, which has dual localization in peroxisomes and mitosomes. Immunoelectron microscopy revealed that Pex14 localized to vesicles of approximately 90–100 nm in diameter. Proteomic analyses of affinity-purified peroxisomes and in silico PTS1 predictions provided datasets of 655 and 56 peroxisomal candidates, respectively; however, only six proteins were shared by both datasets, including myo-inositol dehydrogenase (myo-IDH). Peroxisomal NAD-dependent myo-IDH appeared to be a dimeric enzyme with high affinity to myo-inositol (Km 0.044 mM) and can utilize also scyllo-inositol, D-glucose and D-xylose as substrates. Phylogenetic analyses revealed that orthologs of myo-IDH with PTS1 are present in E. dispar, E. nutalli and E. moshkovskii but not in E. invadens, and form a monophyletic clade of mostly peroxisomal orthologs with free-living Mastigamoeba balamuthi and Pelomyxa schiedti. The presence of peroxisomes in E. histolytica and other archamoebae breaks the paradigm of peroxisome absence in anaerobes and provides a new potential target for the development of antiparasitic drugs.
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Motley, Alison M., Paul C. Galvin, Lakhan Ekal, James M. Nuttall, and Ewald H. Hettema. "Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis." Journal of Cell Biology 211, no. 5 (December 7, 2015): 1041–56. http://dx.doi.org/10.1083/jcb.201412066.
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A recent model for peroxisome biogenesis postulates that peroxisomes form de novo continuously in wild-type cells by heterotypic fusion of endoplasmic reticulum–derived vesicles containing distinct sets of peroxisomal membrane proteins. This model proposes a role in vesicle fusion for the Pex1/Pex6 complex, which has an established role in matrix protein import. The growth and division model proposes that peroxisomes derive from existing peroxisomes. We tested these models by reexamining the role of Pex1/Pex6 and dynamin-related proteins in peroxisome biogenesis. We found that induced depletion of Pex1 blocks the import of matrix proteins but does not affect membrane protein delivery to peroxisomes; markers for the previously reported distinct vesicles colocalize in pex1 and pex6 cells; peroxisomes undergo continued growth if fission is blocked. Our data are compatible with the established primary role of the Pex1/Pex6 complex in matrix protein import and show that peroxisomes in Saccharomyces cerevisiae multiply mainly by growth and division.
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Chang, Chi-Lun, Aubrey V. Weigel, Maria S. Ioannou, H. Amalia Pasolli, C. Shan Xu, David R. Peale, Gleb Shtengel, et al. "Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III." Journal of Cell Biology 218, no. 8 (June 21, 2019): 2583–99. http://dx.doi.org/10.1083/jcb.201902061.
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Lipid droplets (LDs) are neutral lipid storage organelles that transfer lipids to various organelles including peroxisomes. Here, we show that the hereditary spastic paraplegia protein M1 Spastin, a membrane-bound AAA ATPase found on LDs, coordinates fatty acid (FA) trafficking from LDs to peroxisomes through two interrelated mechanisms. First, M1 Spastin forms a tethering complex with peroxisomal ABCD1 to promote LD–peroxisome contact formation. Second, M1 Spastin recruits the membrane-shaping ESCRT-III proteins IST1 and CHMP1B to LDs via its MIT domain to facilitate LD-to-peroxisome FA trafficking, possibly through IST1- and CHMP1B-dependent modifications in LD membrane morphology. Furthermore, LD-to-peroxisome FA trafficking mediated by M1 Spastin is required to relieve LDs of lipid peroxidation. M1 Spastin’s dual roles in tethering LDs to peroxisomes and in recruiting ESCRT-III components to LD–peroxisome contact sites for FA trafficking may underlie the pathogenesis of diseases associated with defective FA metabolism in LDs and peroxisomes.
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Eitzen, Gary A., Rachel K. Szilard, and Richard A. Rachubinski. "Enlarged Peroxisomes Are Present in Oleic Acid–grown Yarrowia lipolytica Overexpressing the PEX16 Gene Encoding an Intraperoxisomal Peripheral Membrane Peroxin." Journal of Cell Biology 137, no. 6 (June 16, 1997): 1265–78. http://dx.doi.org/10.1083/jcb.137.6.1265.
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Pex mutants of the yeast Yarrowia lipolytica are defective in peroxisome assembly. The mutant strain pex16-1 lacks morphologically recognizable peroxisomes. Most peroxisomal proteins are mislocalized to a subcellular fraction enriched for cytosol in pex16 strains, but a subset of peroxisomal proteins is localized at, or near, wild-type levels to a fraction typically enriched for peroxisomes. The PEX16 gene was isolated by functional complementation of the pex16-1 strain and encodes a protein, Pex16p, of 391 amino acids (44,479 D). Pex16p has no known homologues. Pex16p is a peripheral protein located at the matrix face of the peroxisomal membrane. Substitution of the carboxylterminal tripeptide Ser-Thr-Leu, which is similar to the consensus sequence of peroxisomal targeting signal 1, does not affect targeting of Pex16p to peroxisomes. Pex16p is synthesized in wild-type cells grown in glucose-containing media, and its levels are modestly increased by growth of cells in oleic acid–containing medium. Overexpression of the PEX16 gene in oleic acid– grown Y. lipolytica leads to the appearance of a small number of enlarged peroxisomes, which contain the normal complement of peroxisomal proteins at levels approaching those of wild-type peroxisomes.
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Chang, Jinlan, Fred D. Mast, Andrei Fagarasanu, Dorian A. Rachubinski, Gary A. Eitzen, Joel B. Dacks, and Richard A. Rachubinski. "Pex3 peroxisome biogenesis proteins function in peroxisome inheritance as class V myosin receptors." Journal of Cell Biology 187, no. 2 (October 12, 2009): 233–46. http://dx.doi.org/10.1083/jcb.200902117.
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In Saccharomyces cerevisiae, peroxisomal inheritance from mother cell to bud is conducted by the class V myosin motor, Myo2p. However, homologues of S. cerevisiae Myo2p peroxisomal receptor, Inp2p, are not readily identifiable outside the Saccharomycetaceae family. Here, we demonstrate an unexpected role for Pex3 proteins in peroxisome inheritance. Both Pex3p and Pex3Bp are peroxisomal integral membrane proteins that function as peroxisomal receptors for class V myosin through direct interaction with the myosin globular tail. In cells lacking Pex3Bp, peroxisomes are preferentially retained by the mother cell, whereas most peroxisomes gather and are transferred en masse to the bud in cells overexpressing Pex3Bp or Pex3p. Our results reveal an unprecedented role for members of the Pex3 protein family in peroxisome motility and inheritance in addition to their well-established role in peroxisome biogenesis at the endoplasmic reticulum. Our results point to a temporal link between peroxisome formation and inheritance and delineate a general mechanism of peroxisome inheritance in eukaryotic cells.
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Breitling, Rainer, Orzala Sharif, Michelle L. Hartman, and Skaidrite K. Krisans. "Loss of Compartmentalization Causes Misregulation of Lysine Biosynthesis in Peroxisome-Deficient Yeast Cells." Eukaryotic Cell 1, no. 6 (December 2002): 978–86. http://dx.doi.org/10.1128/ec.1.6.978-986.2002.
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ABSTRACT To characterize the metabolic role of peroxisomes in yeast cells under physiological conditions, we performed a comprehensive meta-analysis of published microarray data. Previous studies of yeast peroxisomes have mainly been focused on the function of peroxisomes under extreme conditions, such as growth on oleate or methanol as the sole carbon source, and may therefore not be representative of the normal physiological role of yeast peroxisomes. Surprisingly, our analysis of the microarray data reveals that the only pathway responding to peroxisome deficiency in mid-log phase is lysine biosynthesis, whereas classical peroxisomal pathways such as beta-oxidation are unaffected. We show that the upregulation of lysine biosynthesis genes in peroxisome-deficient yeasts shares many characteristics with the physiological response to lysine starvation. We provide data that suggest that this is the result of a “pathological” stimulation of the Lys14p transcriptional activator by the pathway intermediate aminoadipate semialdehyde. Mistargeting of the peroxisomal lysine pathway to the cytosol increases the active concentration of aminoadipate semialdehyde, which is no longer contained in the peroxisome and can now activate Lys14p at much lower levels than in wild-type yeasts. This is the first well-documented example of pathway misregulation in response to peroxisome deficiency and will be useful in understanding the phenotypic details of human peroxisome-deficient patients (Zellweger syndrome).
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Horiguchi, Hirofumi, Hiroya Yurimoto, Toh-Kheng Goh, Tomoyuki Nakagawa, Nobuo Kato, and Yasuyoshi Sakai. "Peroxisomal Catalase in the Methylotrophic Yeast Candida boidinii: Transport Efficiency and Metabolic Significance." Journal of Bacteriology 183, no. 21 (November 1, 2001): 6372–83. http://dx.doi.org/10.1128/jb.183.21.6372-6383.2001.
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ABSTRACT In this study we cloned CTA1, the gene encoding peroxisomal catalase, from the methylotrophic yeast Candida boidinii and studied targeting of the gene product, Cta1p, into peroxisomes by using green fluorescent protein (GFP) fusion proteins. A strain from which CTA1 was deleted (cta1Δ strain) showed marked growth inhibition when it was grown on the peroxisome-inducing carbon sources methanol, oleate, and d-alanine, indicating that peroxisomal catalase plays an important nonspecific role in peroxisomal metabolism. Cta1p carries a peroxisomal targeting signal type 1 (PTS1) motif, -NKF, in its carboxyl terminus. Using GFP fusion proteins, we found that (i) Cta1p is transported to peroxisomes via its PTS1 motif, -NKF; (ii) peroxisomal localization is necessary for Cta1p to function physiologically; and (iii) Cta1p is bimodally distributed between the cytosol and peroxisomes in methanol-grown cells but is localized exclusively in peroxisomes in oleate- and d-alanine-grown cells. In contrast, the fusion protein GFP-AKL (GFP fused to another typical PTS1 sequence, -AKL), in the context of CbPmp20 andd-amino acid oxidase, was found to localize exclusively in peroxisomes. A yeast two-hybrid system analysis suggested that the low transport efficiency of the -NKF sequence is due to a level of interaction between the -NKF sequence and the PTS1 receptor that is lower than the level of interaction with the AKL sequence. Furthermore, GFP-Cta1pΔnkf coexpressed with Cta1p was successfully localized in peroxisomes, suggesting that the oligomer was formed prior to peroxisome import and that it is not necessary for all four subunits to possess a PTS motif. Since the main physiological function of catalase is degradation of H2O2, suboptimal efficiency of catalase import may confer an evolutionary advantage. We suggest that the PTS1 sequence, which is found in peroxisomal catalases, has evolved in such a way as to give a higher priority for peroxisomal transport to peroxisomal enzymes other than to catalases (e.g., oxidases), which require a higher level of peroxisomal transport efficiency.
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Farelo, Mafalda A., Despoina Korrou-Karava, Katrina F. Brooks, Tiffany A. Russell, Kevin Maringer, and Peter U. Mayerhofer. "Dengue and Zika Virus Capsid Proteins Contain a Common PEX19-Binding Motif." Viruses 14, no. 2 (January 27, 2022): 253. http://dx.doi.org/10.3390/v14020253.
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Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have evolved sophisticated mechanisms to suppress the host immune system. For instance, flavivirus infections were found to sabotage peroxisomes, organelles with an important role in innate immunity. The current model suggests that the capsid (C) proteins of DENV and ZIKV downregulate peroxisomes, ultimately resulting in reduced production of interferons by interacting with the host protein PEX19, a crucial chaperone in peroxisomal biogenesis. Here, we aimed to explore the importance of peroxisomes and the role of C interaction with PEX19 in the flavivirus life cycle. By infecting cells lacking peroxisomes we show that this organelle is required for optimal DENV replication. Moreover, we demonstrate that DENV and ZIKV C bind PEX19 through a conserved PEX19-binding motif, which is also commonly found in cellular peroxisomal membrane proteins (PMPs). However, in contrast to PMPs, this interaction does not result in the targeting of C to peroxisomes. Furthermore, we show that the presence of C results in peroxisome loss due to impaired peroxisomal biogenesis, which appears to occur by a PEX19-independent mechanism. Hence, these findings challenge the current model of how flavivirus C might downregulate peroxisomal abundance and suggest a yet unknown role of peroxisomes in flavivirus biology.
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Hosoi, Ken-ichiro, Non Miyata, Satoru Mukai, Satomi Furuki, Kanji Okumoto, Emily H. Cheng, and Yukio Fujiki. "The VDAC2–BAK axis regulates peroxisomal membrane permeability." Journal of Cell Biology 216, no. 3 (February 7, 2017): 709–22. http://dx.doi.org/10.1083/jcb.201605002.
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Peroxisomal biogenesis disorders (PBDs) are fatal genetic diseases consisting of 14 complementation groups (CGs). We previously isolated a peroxisome-deficient Chinese hamster ovary cell mutant, ZP114, which belongs to none of these CGs. Using a functional screening strategy, VDAC2 was identified as rescuing the peroxisomal deficiency of ZP114 where VDAC2 expression was not detected. Interestingly, knockdown of BAK or overexpression of the BAK inhibitors BCL-XL and MCL-1 restored peroxisomal biogenesis in ZP114 cells. Although VDAC2 is not localized to the peroxisome, loss of VDAC2 shifts the localization of BAK from mitochondria to peroxisomes, resulting in peroxisomal deficiency. Introduction of peroxisome-targeted BAK harboring the Pex26p transmembrane region into wild-type cells resulted in the release of peroxisomal matrix proteins to cytosol. Moreover, overexpression of BAK activators PUMA and BIM permeabilized peroxisomes in a BAK-dependent manner. Collectively, these findings suggest that BAK plays a role in peroxisomal permeability, similar to mitochondrial outer membrane permeabilization.
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Nair, Devi M., P. Edward Purdue, and Paul B. Lazarow. "Pex7p translocates in and out of peroxisomes in Saccharomyces cerevisiae." Journal of Cell Biology 167, no. 4 (November 15, 2004): 599–604. http://dx.doi.org/10.1083/jcb.200407119.
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Pex7p is the soluble receptor responsible for importing into peroxisomes newly synthesized proteins bearing a type 2 peroxisomal targeting sequence. We observe that appending GFP to Pex7p's COOH terminus shifts Pex7p's intracellular distribution from predominantly cytosolic to predominantly peroxisomal in Saccharomyces cerevisiae. Cleavage of the link between Pex7p and GFP within peroxisomes liberates GFP, which remains inside the organelle, and Pex7p, which exits to the cytosol. The reexported Pex7p is functional, resulting in import of thiolase into peroxisomes and improved growth of the yeast on oleic acid. These results support the “extended shuttle” model of peroxisome import receptor function and open the way to future studies of receptor export.
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MENDIS‐HANDAGAMA, S. M. L. CHAMINDRANI, BARRY R. ZIRKIN, TERRENCE J. SCALLEN, and LARRY L. EWING. "Studies on Peroxisomes of the Adult Rat Leydig Cell." Journal of Andrology 11, no. 3 (May 6, 1990): 270–78. http://dx.doi.org/10.1002/j.1939-4640.1990.tb03239.x.
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The aims of this study were to differentially identify peroxisomes and lysosomes in Leydig cells of the sexually mature rat using cytochemical techniques, to describe the size and shape of peroxisomal profiles, and to localize catalase and sterol carrier protein‐2 (SCP2) in Leydig cell peroxisomes. Peroxisome profiles, identified by cytochemical staining for catalase activity using 3,3′‐diaminobenzidine tetrahydrochloride (DAB) were categorized according to their longest diameter as small (less than 0.18 μm), intermediate (0.18–0.45 μm), and large (more than 0.45 μm); and according to their shape, which were designated as circular, oval, and dumbbell. Together these peroxisomal profiles occupied 11.2 μm3/Leydig cell. Lysosomes, identified in the same tissue sections as acid phosphatase positive organelles, occupied 12.9 μm3/Leydig cell. Negative bodies with morphology identical to cytochemically unstained peroxisomes also were detected. These organelles occupied 14.5 μm3/Leydig cell. Catalase was immunolocalized exclusively in Leydig cell peroxisomes using AuroProbe EM protein A G10 (ie, 10 nm gold particles). Sterol carrier protein‐2 was immunolocalized in Leydig cell peroxisomes by AuroProbe EM protein A G15 (ie, 15 nm gold particles). Immunolocalization of catalase and SCP2 using 10 nm and 15 nm gold particles in the same peroxisomes confirmed that Leydig cell peroxisomes contain SCP2. Taken together, these results show conclusively that adult rat Leydig cell peroxisomal profiles occur in different shapes and sizes, which suggests the existence of a network of peroxisomes, rather than peroxisomes occurring as separate isolated organelles. More importantly, the present study demonstrates for the first time that Leydig cell peroxisomes contain SCP2. The fact that Leydig cell peroxisomes contain SCP2, suggests that they may be involved in LH stimulated Leydig cell testosterone production.
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Vizeacoumar, Franco J., Juan C. Torres-Guzman, Yuen Yi C. Tam, John D. Aitchison, and Richard A. Rachubinski. "YHR150w and YDR479c encode peroxisomal integral membrane proteins involved in the regulation of peroxisome number, size, and distribution in Saccharomyces cerevisiae." Journal of Cell Biology 161, no. 2 (April 21, 2003): 321–32. http://dx.doi.org/10.1083/jcb.200210130.
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The peroxin Pex24p of the yeast Yarrowia lipolytica exhibits high sequence similarity to two hypothetical proteins, Yhr150p and Ydr479p, encoded by the Saccharomyces cerevisiae genome. Like YlPex24p, both Yhr150p and Ydr479p have been shown to be integral to the peroxisomal membrane, but unlike YlPex24p, their levels of synthesis are not increased upon a shift of cells from glucose- to oleic acid–containing medium. Peroxisomes of cells deleted for either or both of the YHR150w and YDR479c genes are increased in number, exhibit extensive clustering, are smaller in area than peroxisomes of wild-type cells, and often exhibit membrane thickening between adjacent peroxisomes in a cluster. Peroxisomes isolated from cells deleted for both genes have a decreased buoyant density compared with peroxisomes isolated from wild-type cells and still exhibit clustering and peroxisomal membrane thickening. Overexpression of the genes PEX25 or VPS1, but not the gene PEX11, restored the wild-type phenotype to cells deleted for one or both of the YHR150w and YDR479c genes. Together, our data suggest a role for Yhr150p and Ydr479p, together with Pex25p and Vps1p, in regulating peroxisome number, size, and distribution in S. cerevisiae. Because of their role in peroxisome dynamics, YHR150w and YDR479c have been designated as PEX28 and PEX29, respectively, and their encoded peroxins as Pex28p and Pex29p.
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Escaño, Cristopher Salazar, Praveen Rao Juvvadi, Feng Jie Jin, Tadashi Takahashi, Yasuji Koyama, Shuichi Yamashita, Jun-ichi Maruyama, and Katsuhiko Kitamoto. "Disruption of the Aopex11-1 Gene Involved in Peroxisome Proliferation Leads to Impaired Woronin Body Formation in Aspergillus oryzae." Eukaryotic Cell 8, no. 3 (January 9, 2009): 296–305. http://dx.doi.org/10.1128/ec.00197-08.
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ABSTRACT The Woronin body, a unique organelle found in the Pezizomycotina, plugs the septal pore upon hyphal damage to prevent excessive cytoplasmic bleeding. Although it was previously shown that the Woronin body buds out from the peroxisome, the relationship between peroxisomal proliferation/division and Woronin body differentiation has not been extensively investigated. In this report, we examined whether Pex11 required for peroxisomal proliferation participates in Woronin body formation in Aspergillus oryzae. A. oryzae contained two orthologous PEX11 genes that were designated Aopex11-1 and Aopex11-2. Deletion of Aopex11 genes revealed that only the ΔAopex11-1 strain showed reduced growth and enlarged peroxisomes in the presence of oleic acid as a sole carbon source, indicating a defect in peroxisomal function and proliferation. Disruption of Aopex11-1 gene impaired the Woronin body function, leading to excessive loss of the cytosol upon hyphal injury. Dual localization analysis of the peroxisome and Woronin body protein AoHex1 demonstrated that Woronin bodies fail to fully differentiate from peroxisomes in the ΔAopex11-1 strain. Furthermore, distribution of AoHex1 was found to be peripheral in the enlarged peroxisome or junctional in dumbbell-shaped peroxisomes. Electron microscopy of the ΔAopex11-1 strain revealed the presence of Woronin bodies that remained associated with organelles resembling peroxisomes, which was supported from the sucrose gradient centrifugation confirming that the Woronin body protein AoHex1 overlapped with the density-shifted peroxisome in the ΔAopex11-1 strain. In conclusion, the present study describes the role of Pex11 in Woronin body differentiation for the first time.
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Chalermwat, Chalongchai, Thitipa Thosapornvichai, Laran T. Jensen, and Duangrurdee Wattanasirichaigoon. "Genetic Analysis of Peroxisomal Genes Required for Longevity in a Yeast Model of Citrin Deficiency." Diseases 8, no. 1 (January 9, 2020): 2. http://dx.doi.org/10.3390/diseases8010002.
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Citrin is a liver-specific mitochondrial aspartate–glutamate carrier encoded by SLC25A13. Citrin deficiency caused by SLC25A13 mutation results in carbohydrate toxicity, citrullinemia type II, and fatty liver diseases, the mechanisms of some of which remain unknown. Citrin shows a functional homolog in yeast aspartate-glutamate carrier (Agc1p) and agc1Δ yeasts are used as a model organism of citrin deficiency. Here, we found that agc1Δ yeasts decreased fat utilization, impaired NADH balance in peroxisomes, and decreased chronological lifespan. The activation of GPD1-mediated NAD+ regeneration in peroxisomes by GPD1 over-expression or activation of the malate–oxaloacetate NADH peroxisomal shuttle, by increasing flux in this NADH shuttle and over-expression of MDH3, resulted in lifespan extension of agc1Δ yeasts. In addition, over-expression of PEX34 restored longevity of agc1Δ yeasts as well as wild-type cells. The effect of PEX34-mediated longevity required the presence of the GPD1-mediated NADH peroxisomal shuttle, which was independent of the presence of the peroxisomal malate–oxaloacetate NADH shuttle and PEX34-induced peroxisome proliferation. These data confirm that impaired NAD+ regeneration in peroxisomes is a key defect in the yeast model of citrin deficiency, and enhancing peroxisome function or inducing NAD+ regeneration in peroxisomes is suggested for further study in patients’ hepatocytes.
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Wanders, R. J. A., E. G. van Grunsven, and G. A. Jansen. "Lipid metabolism in peroxisomes: enzymology, functions and dysfunctions of the fatty acid α- and β-oxidation systems in humans." Biochemical Society Transactions 28, no. 2 (February 1, 2000): 141–49. http://dx.doi.org/10.1042/bst0280141.
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Peroxisomes are subcellular organelles present in virtually all eukaryotic cells catalysing a number of indispensable functions in cellular metabolism. The importance of peroxisomes in man is stressed by the existence of an expanding group of genetic diseases in which there is an impairment in one or more peroxisomal functions. One of the major functions of peroxisomes concerns their role in lipid metabolism, which includes: (i) fatty acid β-oxidation; (ii) ether phospholipid synthesis; (iii) fatty acid α-oxidation; and (iv) isoprenoid biosynthesis. In this paper, we review the current state of knowledge concerning the peroxisomal fatty acid α- and β-oxidation systems with particular emphasis on the enzymes involved and the various disorders of fatty acid oxidation in peroxisomes. We also pay attention to the fact that some of the metabolites that accumulate as the result of a defect in peroxisomal α- and/or β-oxidation are activators of members of the family of nuclear receptors, including peroxisome-proliferator-act-ivated receptor α.
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Léon, Sébastien, Lan Zhang, W. Hayes McDonald, John Yates, James M. Cregg, and Suresh Subramani. "Dynamics of the peroxisomal import cycle of PpPex20p: Ubiquitin-dependent localization and regulation." Journal of Cell Biology 172, no. 1 (January 2, 2006): 67–78. http://dx.doi.org/10.1083/jcb.200508096.
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We characterize the peroxin PpPex20p from Pichia pastoris and show its requirement for translocation of PTS2 cargoes into peroxisomes. PpPex20p docks at the peroxisomal membrane and translocates into peroxisomes. Its peroxisomal localization requires the docking peroxin Pex14p but not the peroxins Pex2p, Pex10p, and Pex12p, whose absence causes peroxisomal accumulation of Pex20p. Similarities between Pex5p and Pex20p were noted in their protein interactions and dynamics during import, and both contain a conserved NH2-terminal domain. In the absence of the E2-like Pex4p or the AAA proteins Pex1p and Pex6p, Pex20p is degraded via polyubiquitylation of residue K19, and the K19R mutation causes accumulation of Pex20p in peroxisome remnants. Finally, either interference with K48-branched polyubiquitylation or removal of the conserved NH2-terminal domain causes accumulation of Pex20p in peroxisomes, mimicking a defect in its recycling to the cytosol. Our data are consistent with a model in which Pex20p enters peroxisomes and recycles back to the cytosol in an ubiquitin-dependent manner.
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Koch, Annett, Yisang Yoon, Nina A. Bonekamp, Mark A. McNiven, and Michael Schrader. "A Role for Fis1 in Both Mitochondrial and Peroxisomal Fission in Mammalian Cells." Molecular Biology of the Cell 16, no. 11 (November 2005): 5077–86. http://dx.doi.org/10.1091/mbc.e05-02-0159.
Full textAbstract:
The mammalian dynamin-like protein DLP1/Drp1 has been shown to mediate both mitochondrial and peroxisomal fission. In this study, we have examined whether hFis1, a mammalian homologue of yeast Fis1, which has been shown to participate in mitochondrial fission by an interaction with DLP1/Drp1, is also involved in peroxisomal growth and division. We show that hFis1 localizes to peroxisomes in addition to mitochondria. Through differential tagging and deletion experiments, we demonstrate that the transmembrane domain and the short C-terminal tail of hFis1 is both necessary and sufficient for its targeting to peroxisomes and mitochondria, whereas the N-terminal region is required for organelle fission. hFis1 promotes peroxisome division upon ectopic expression, whereas silencing of Fis1 by small interfering RNA inhibited fission and caused tubulation of peroxisomes. These findings provide the first evidence for a role of Fis1 in peroxisomal fission and suggest that the fission machinery of mitochondria and peroxisomes shares common components.
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Perry, Ryan J., Fred D. Mast, and Richard A. Rachubinski. "Endoplasmic Reticulum-Associated Secretory Proteins Sec20p, Sec39p, and Dsl1p Are Involved in Peroxisome Biogenesis." Eukaryotic Cell 8, no. 6 (April 3, 2009): 830–43. http://dx.doi.org/10.1128/ec.00024-09.
Full textAbstract:
ABSTRACT Two pathways have been identified for peroxisome formation: (i) growth and division and (ii) de novo synthesis. Recent experiments determined that peroxisomes originate at the endoplasmic reticulum (ER). Although many proteins have been implicated in the peroxisome biogenic program, no proteins in the eukaryotic secretory pathway have been identified as having roles in peroxisome formation. Using the yeast Saccharomyces cerevisiae regulatable Tet promoter Hughes clone collection, we found that repression of the ER-associated secretory proteins Sec20p and Sec39p resulted in mislocalization of the peroxisomal matrix protein chimera Pot1p-green fluorescent protein (GFP) to the cytosol. Likewise, the peroxisomal membrane protein chimera Pex3p-GFP localized to tubular-vesicular structures in cells suppressed for Sec20p, Sec39p, and Dsl1p, which form a complex at the ER. Loss of Sec39p attenuated formation of Pex3p-derived peroxisomal structures following galactose induction of Pex3p-GFP expression from the GAL1 promoter. Expression of Sec20p, Sec39p, and Dsl1p was moderately increased in yeast grown under conditions that proliferate peroxisomes, and Sec20p, Sec39p, and Dsl1p were found to cofractionate with peroxisomes and colocalize with Pex3p-monomeric red fluorescent protein under these conditions. Our results show that SEC20, SEC39, and DSL1 are essential secretory genes involved in the early stages of peroxisome assembly, and this work is the first to identify and characterize an ER-associated secretory machinery involved in peroxisome biogenesis.
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MUELLER, Sebastian, Angelika WEBER, Reiner FRITZ, Sabine MÜTZE, Daniel ROST, Henning WALCZAK, Alfred VÖLKL, and Wolfgang STREMMEL. "Sensitive and real-time determination of H2O2 release from intact peroxisomes." Biochemical Journal 363, no. 3 (April 24, 2002): 483–91. http://dx.doi.org/10.1042/bj3630483.
Full textAbstract:
Peroxisomes are essential and ubiquitous cell organelles having a key role in mammalian lipid and oxygen metabolism. The presence of flavine oxidases makes them an important intracellular source of H2O2: an obligate product of peroxisomal redox reactions and a key reactive oxygen species. Peroxisomes proliferate in response to external signals triggered by peroxisome-proliferator-activated receptor signalling pathways. Peroxisome-derived oxidative stress as a consequence of this proliferation is increasingly recognized to participate in pathologies ranging from carcinogenesis in rodents to alcoholic and non-alcoholic steatosis hepatitis in humans. To date, no sensitive approach exists to record H2O2 turnover of peroxisomes in real time. Here, we introduce a sensitive chemiluminescence method that allows the monitoring of H2O2 generation and degradation in real time in suspensions of intact peroxisomes. Importantly, removal, as well as release of, H2O2 can be assessed at nanomolar, non-toxic concentrations in the same sample. Owing to the kinetic properties of catalase and oxidases, H2O2 forms fast steady-state concentrations in the presence of various peroxisomal substrates. Substrate screening suggests that urate, glycolate and activated fatty acids are the most important sources for H2O2 in rodents. Kinetic studies imply further that peroxisomes contribute significantly to the β-oxidation of medium-chain fatty acids, in addition to their essential role in the breakdown of long and very long ones. These observations establish a direct quantitative release of H2O2 from intact peroxisomes. The experimental approach offers new possibilities for functionally studying H2O2 metabolism, substrate transport and turnover in peroxisomes of eukaryotic cells.
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Hashiguchi, Noriyo, Tomoko Kojidani, Tsuneo Imanaka, Tokuko Haraguchi, Yasushi Hiraoka, Eveline Baumgart, Sadaki Yokota, Toshiro Tsukamoto, and Takashi Osumi. "Peroxisomes Are Formed from Complex Membrane Structures inPEX6-deficient CHO Cells upon Genetic Complementation." Molecular Biology of the Cell 13, no. 2 (February 2002): 711–22. http://dx.doi.org/10.1091/mbc.01-10-0479.
Full textAbstract:
Pex6p belongs to the AAA family of ATPases. Its CHO mutant, ZP92, lacks normal peroxisomes but contains peroxisomal membrane remnants, so called peroxisomal ghosts, which are detected with anti–70-kDa peroxisomal membrane protein (PMP70) antibody. No peroxisomal matrix proteins were detected inside the ghosts, but exogenously expressed green fluorescent protein (GFP) fused to peroxisome targeting signal-1 (PTS-1) accumulated in the areas adjacent to the ghosts. Electron microscopic examination revealed that PMP70-positive ghosts in ZP92 were complex membrane structures, rather than peroxisomes with reduced matrix protein import ability. In a typical case, a set of one central spherical body and two layers of double-membraned loops were observed, with endoplasmic reticulum present alongside the outer loop. In the early stage of complementation by PEX6 cDNA, catalase and acyl-CoA oxidase accumulated in the lumen of the double-membraned loops. Biochemical analysis revealed that almost all the peroxisomal ghosts were converted into peroxisomes upon complementation. Our results indicate that 1) Peroxisomal ghosts are complex membrane structures; and 2) The complex membrane structures become import competent and are converted into peroxisomes upon complementation with PEX6.
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Collings, David A., John DI Harper, Jan Marc, Robyn L. Overall, and Robert T. Mullen. "Life in the fast lane: actin-based motility of plant peroxisomes." Canadian Journal of Botany 80, no. 4 (April 1, 2002): 430–41. http://dx.doi.org/10.1139/b02-036.
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Peroxisomal shape, distribution, motility, and interactions with cytoskeletal elements were examined during interphase in living leek (Allium porrum L.) epidermal cells transiently transformed with a construct encoding the green fluorescent protein bearing a carboxy-terminal type 1 peroxisomal targeting signal. Confocal laser scanning microscopy and time-course analysis revealed that labeled peroxisomes were either spherical or rod-shaped and possessed several types of motility including random oscillations, slow and fast directional and bidirectional movements, and stop-and-go movements. Co-localization studies indicated that most peroxisomes were in close association with actin filaments, while treatment of cells with the actin-disrupting drug cytochalasin D blocked all types of peroxisomal movements. In contrast, the overall spatial organization of peroxisomes and the microtubule cytoskeleton were different, and the microtubule-destabilizing agent oryzalin had no obvious effect on peroxisomal motility. These data indicate that the peroxisome in plant cells is a highly dynamic compartment that is dependent upon the actin cytoskeleton, not microtubules, for its subcellular distribution and movements.Key words: actin filaments, cytoskeleton, green fluorescent protein, leek, microtubules, peroxisomes.
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Szilard, R. K., V. I. Titorenko, M. Veenhuis, and R. A. Rachubinski. "Pay32p of the yeast Yarrowia lipolytica is an intraperoxisomal component of the matrix protein translocation machinery." Journal of Cell Biology 131, no. 6 (December 15, 1995): 1453–69. http://dx.doi.org/10.1083/jcb.131.6.1453.
Full textAbstract:
Pay mutants of the yeast Yarrowia lipolytica fail to assemble functional peroxisomes. One mutant strain, pay32-1, has abnormally small peroxisomes that are often found in clusters surrounded by membraneous material. The functionally complementing gene PAY32 encodes a protein, Pay32p, of 598 amino acids (66,733 D) that is a member of the tetratricopeptide repeat family. Pay32p is intraperoxisomal. In wild-type peroxisomes, Pay32p is associated primarily with the inner surface of the peroxisomal membrane, but approximately 30% of Pay32p is localized to the peroxisomal matrix. The majority of Pay32p in the matrix is complexed with two polypeptides of 62 and 64 kD recognized by antibodies to SKL (peroxisomal targeting signal-1). In contrast, in peroxisomes of the pay32-1 mutant, Pay32p is localized exclusively to the matrix and forms no complex. Biochemical characterization of the mutants pay32-1 and pay32-KO (a PAY32 gene disruption strain) showed that Pay32p is a component of the peroxisomal translocation machinery. Mutations in the PAY32 gene prevent the translocation of most peroxisome-bound proteins into the peroxisomal matrix. These proteins, including the 62-kD anti-SKL-reactive polypeptide, are trapped in the peroxisomal membrane at an intermediate stage of translocation in pay32 mutants. Our results suggest that there are at least two distinct translocation machineries involved in the import of proteins into peroxisomes.
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Lambkin, Gareth R., and Richard A. Rachubinski. "Yarrowia lipolyticaCells Mutant for the Peroxisomal Peroxin Pex19p Contain Structures Resembling Wild-Type Peroxisomes." Molecular Biology of the Cell 12, no. 11 (November 2001): 3353–64. http://dx.doi.org/10.1091/mbc.12.11.3353.
Full textAbstract:
PEX genes encode peroxins, which are proteins required for peroxisome assembly. The PEX19 gene of the yeast Yarrowia lipolytica was isolated by functional complementation of the oleic acid-nonutilizing strainpex19-1 and encodes Pex19p, a protein of 324 amino acids (34,822 Da). Subcellular fractionation and immunofluorescence microscopy showed Pex19p to be localized primarily to peroxisomes. Pex19p is detected in cells grown in glucose-containing medium, and its levels are not increased by incubation of cells in oleic acid–containing medium, the metabolism of which requires intact peroxisomes. pex19 cells preferentially mislocalize peroxisomal matrix proteins and the peripheral intraperoxisomal membrane peroxin Pex16p to the cytosol, although small amounts of these proteins could be reproducibly localized to a subcellular fraction enriched for peroxisomes. In contrast, the peroxisomal integral membrane protein Pex2p exhibits greatly reduced levels inpex19 cells compared with its levels in wild-type cells. Importantly, pex19 cells were shown by electron microscopy to contain structures that resemble wild-type peroxisomes in regards to size, shape, number, and electron density. Subcellular fractionation and isopycnic density gradient centrifugation confirmed the presence of vesicular structures in pex19 mutant strains that were similar in density to wild-type peroxisomes and that contained profiles of peroxisomal matrix and membrane proteins that are similar to, yet distinct from, those of wild-type peroxisomes. Because peroxisomal structures form in pex19 cells, Pex19p apparently does not function as a peroxisomal membrane protein receptor in Y. lipolytica. Our results are consistent with a role for Y. lipolytica Pex19p in stabilizing the peroxisomal membrane.
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Jo, Doo Sin, Na Yeon Park, and Dong-Hyung Cho. "Peroxisome quality control and dysregulated lipid metabolism in neurodegenerative diseases." Experimental & Molecular Medicine 52, no. 9 (September 2020): 1486–95. http://dx.doi.org/10.1038/s12276-020-00503-9.
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Abstract In recent decades, the role of the peroxisome in physiology and disease conditions has become increasingly important. Together with the mitochondria and other cellular organelles, peroxisomes support key metabolic platforms for the oxidation of various fatty acids and regulate redox conditions. In addition, peroxisomes contribute to the biosynthesis of essential lipid molecules, such as bile acid, cholesterol, docosahexaenoic acid, and plasmalogen. Therefore, the quality control mechanisms that regulate peroxisome biogenesis and degradation are important for cellular homeostasis. Current evidence indicates that peroxisomal function is often reduced or dysregulated in various human disease conditions, such as neurodegenerative diseases. Here, we review the recent progress that has been made toward understanding the quality control systems that regulate peroxisomes and their pathological implications.
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Liu, Xu, Xin Wen, and Daniel J. Klionsky. "Endoplasmic Reticulum–Mitochondria Contacts Are Required for Pexophagy in Saccharomyces cerevisiae." Contact 2 (January 2019): 251525641882158. http://dx.doi.org/10.1177/2515256418821584.
Full textAbstract:
Peroxisomes play important roles in lipid metabolism. Surplus or damaged peroxisomes can be selectively targeted for autophagic degradation, a process termed pexophagy. Maintaining a proper level of pexophagy is critical for cellular homeostasis. Here, we found that endoplasmic reticulum (ER)–mitochondria contact sites are necessary for efficient pexophagy. During pexophagy, the peroxisomes destined for degradation are adjacent to the ER–mitochondria encounter structure (ERMES) that mediates the formation of ER–mitochondria contacts; disruption of the ERMES results in a severe defect in pexophagy. We show that a mutant form of Mdm34, a component of the ERMES, which impairs ERMES formation and diminishes its association with the peroxisomal membrane protein Pex11, also causes defects in pexophagy. The dynamin-related GTPase Vps1, which is specific for peroxisomal fission, is recruited to the peroxisomes at ER–mitochondria contacts by the selective autophagy scaffold Atg11 and the pexophagy receptor Atg36, facilitating peroxisome degradation.
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Erdmann, R., and G. Blobel. "Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p." Journal of Cell Biology 128, no. 4 (February 15, 1995): 509–23. http://dx.doi.org/10.1083/jcb.128.4.509.
Full textAbstract:
We have purified peroxisomal membranes from Saccharomyces cerevisiae after induction of peroxisomes in oleic acid-containing media. About 30 distinct proteins could be discerned among the HPLC- and SDS-PAGE-separated proteins of the high salt-extracted peroxisomal membranes. The most abundant of these, Pmp27p, was purified and the corresponding gene PMP27 was cloned and sequenced. Its primary structure is 32% identical to PMP31 and PMP32 of the yeast Candida biodinii (Moreno, M., R. Lark, K. L. Campbell, and M. J. Goodman. 1994. Yeast. 10:1447-1457). Immunoelectron microscopic localization of Pmp27p showed labeling of the peroxisomal membrane, but also of matrix-less and matrix containing tubular membranes nearby. Electronmicroscopical data suggest that some of these tubular extensions might interconnect peroxisomes to form a peroxisomal reticulum. Cells with a disrupted PMP27 gene (delta pmp27) still grew well on glucose or ethanol, but they failed to grow on oleate although peroxisomes were still induced by transfer to oleate-containing media. The induced peroxisomes of delta pmp27 cells were fewer but considerably larger than those of wild-type cells, suggesting that Pmp27p may be involved in parceling of peroxisomes into regular quanta. delta pmp27 cells cultured in oleate-containing media form multiple buds, of which virtually all are peroxisome deficient. The growth defect of delta pmp27 cells on oleic acid appears to result from the inability to segregate the giant peroxisomes to daughter cells.
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Hua, Rong, Derrick Cheng, Étienne Coyaud, Spencer Freeman, Erminia Di Pietro, Yuqing Wang, Adriano Vissa, et al. "VAPs and ACBD5 tether peroxisomes to the ER for peroxisome maintenance and lipid homeostasis." Journal of Cell Biology 216, no. 2 (January 20, 2017): 367–77. http://dx.doi.org/10.1083/jcb.201608128.
Full textAbstract:
Lipid exchange between the endoplasmic reticulum (ER) and peroxisomes is necessary for the synthesis and catabolism of lipids, the trafficking of cholesterol, and peroxisome biogenesis in mammalian cells. However, how lipids are exchanged between these two organelles is not understood. In this study, we report that the ER-resident VAMP-associated proteins A and B (VAPA and VAPB) interact with the peroxisomal membrane protein acyl-CoA binding domain containing 5 (ACBD5) and that this interaction is required to tether the two organelles together, thereby facilitating the lipid exchange between them. Depletion of either ACBD5 or VAP expression results in increased peroxisome mobility, suggesting that VAP–ACBD5 complex acts as the primary ER–peroxisome tether. We also demonstrate that tethering of peroxisomes to the ER is necessary for peroxisome growth, the synthesis of plasmalogen phospholipids, and the maintenance of cellular cholesterol levels. Collectively, our data highlight the importance of VAP–ACBD5–mediated contact between the ER and peroxisomes for organelle maintenance and lipid homeostasis.