Academic literature on the topic 'Dynamin Related Protein 1 (Drp1)'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Dynamin Related Protein 1 (Drp1).'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Journal articles on the topic "Dynamin Related Protein 1 (Drp1)"
1
Perry, Heather M., Liping Huang, Rebecca J. Wilson, Amandeep Bajwa, Hiromi Sesaki, Zhen Yan, Diane L. Rosin, David F. Kashatus, and Mark D. Okusa. "Dynamin-Related Protein 1 Deficiency Promotes Recovery from AKI." Journal of the American Society of Nephrology 29, no. 1 (October 30, 2017): 194–206. http://dx.doi.org/10.1681/asn.2017060659.
Full textAbstract:
The proximal tubule epithelium relies on mitochondrial function for energy, rendering the kidney highly susceptible to ischemic AKI. Dynamin-related protein 1 (DRP1), a mediator of mitochondrial fission, regulates mitochondrial function; however, the cell-specific and temporal role of DRP1 in AKI in vivo is unknown. Using genetic murine models, we found that proximal tubule–specific deletion of Drp1 prevented the renal ischemia-reperfusion–induced kidney injury, inflammation, and programmed cell death observed in wild-type mice and promoted epithelial recovery, which associated with activation of the renoprotective β-hydroxybutyrate signaling pathway. Loss of DRP1 preserved mitochondrial structure and reduced oxidative stress in injured kidneys. Lastly, proximal tubule deletion of DRP1 after ischemia-reperfusion injury attenuated progressive kidney injury and fibrosis. These results implicate DRP1 and mitochondrial dynamics as an important mediator of AKI and progression to fibrosis and suggest that DRP1 may serve as a therapeutic target for AKI.
2
Breitzig, Mason T., Matthew D. Alleyn, Richard F. Lockey, and Narasaiah Kolliputi. "A mitochondrial delicacy: dynamin-related protein 1 and mitochondrial dynamics." American Journal of Physiology-Cell Physiology 315, no. 1 (July 1, 2018): C80—C90. http://dx.doi.org/10.1152/ajpcell.00042.2018.
Full textAbstract:
The constant physiological flux of mitochondrial fission and fusion is inextricably tied to the maintenance of cellular bioenergetics and the fluidity of mitochondrial networks. Yet, the intricacies of this dynamic duo remain unclear in diseases that encompass mitochondrial dysregulation. Particularly, the role of the GTPase fission protein dynamin-related protein 1 (Drp1) is of profound interest. Studies have identified that Drp1 participates in complex signaling pathways, suggesting that the function of mitochondria in pathophysiology may extend far beyond energetics alone. Research indicates that, in stressed conditions, Drp1 translocation to the mitochondria leads to elevated fragmentation and mitophagy; however, despite this, there is limited knowledge about the mechanistic regulation of Drp1 in disease conditions. This review highlights literature about fission, fusion, and, more importantly, discusses Drp1 in cardiac, neural, carcinogenic, renal, and pulmonary diseases. The therapeutic desirability for further research into its contribution to diseases that involve mitochondrial dysregulation is also discussed.
3
Ugarte-Uribe, Begoña, Hans-Michael Müller, Miki Otsuki, Walter Nickel, and Ana J. García-Sáez. "Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division." Journal of Biological Chemistry 289, no. 44 (September 18, 2014): 30645–56. http://dx.doi.org/10.1074/jbc.m114.575779.
Full textAbstract:
Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reconstituted and directly visualized Drp1 activity in giant unilamellar vesicles. We quantified the effect of lipid composition and GTP on membrane binding and remodeling activity by fluorescence confocal microscopy and flow cytometry. In contrast to other dynamin relatives, Drp1 bound to both curved and flat membranes even in the absence of nucleotides. We also found that Drp1 induced membrane tubulation that was stimulated by cardiolipin. Moreover, Drp1 promoted membrane tethering dependent on the intrinsic curvature of the membrane lipids and on GTP. Interestingly, Drp1 concentrated at membrane contact surfaces and, in the presence of GTP, formed discrete clusters on the vesicles. Our findings support a role of Drp1 not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission.
4
Oliver, Darryll, and P. Reddy. "Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases." Cells 8, no. 9 (August 23, 2019): 961. http://dx.doi.org/10.3390/cells8090961.
Full textAbstract:
The purpose of this article is to highlight the role of dynamin-related protein 1 (Drp1) in abnormal mitochondrial dynamics, mitochondrial fragmentation, autophagy/mitophagy, and neuronal damage in Alzheimer’s disease (AD) and other neurological diseases, including Parkinson’s, Huntington’s, amyotrophic lateral sclerosis, multiple sclerosis, diabetes, and obesity. Dynamin-related protein 1 is one of the evolutionarily highly conserved large family of GTPase proteins. Drp1 is critical for mitochondrial division, size, shape, and distribution throughout the neuron, from cell body to axons, dendrites, and nerve terminals. Several decades of intense research from several groups revealed that Drp1 is enriched at neuronal terminals and involved in synapse formation and synaptic sprouting. Different phosphorylated forms of Drp1 acts as both increased fragmentation and/or increased fusion of mitochondria. Increased levels of Drp1 were found in diseased states and caused excessive fragmentation of mitochondria, leading to mitochondrial dysfunction and neuronal damage. In the last two decades, several Drp1 inhibitors have been developed, including Mdivi-1, Dynasore, P110, and DDQ and their beneficial effects tested using cell cultures and mouse models of neurodegenerative diseases. Recent research using genetic crossing studies revealed that a partial reduction of Drp1 is protective against mutant protein(s)-induced mitochondrial and synaptic toxicities. Based on findings from cell cultures, mouse models and postmortem brains of AD and other neurodegenerative disease, we cautiously conclude that reduced Drp1 is a promising therapeutic target for AD and other neurological diseases.
5
Strack, Stefan, Theodore J. Wilson, and J. Thomas Cribbs. "Cyclin-dependent kinases regulate splice-specific targeting of dynamin-related protein 1 to microtubules." Journal of Cell Biology 201, no. 7 (June 24, 2013): 1037–51. http://dx.doi.org/10.1083/jcb.201210045.
Full textAbstract:
Fission and fusion reactions determine mitochondrial morphology and function. Dynamin-related protein 1 (Drp1) is a guanosine triphosphate–hydrolyzing mechanoenzyme important for mitochondrial fission and programmed cell death. Drp1 is subject to alternative splicing of three exons with previously unknown functional significance. Here, we report that splice variants including the third but excluding the second alternative exon (x01) localized to and copurified with microtubule bundles as dynamic polymers that resemble fission complexes on mitochondria. A major isoform in immune cells, Drp1-x01 required oligomeric assembly and Arg residues in alternative exon 3 for microtubule targeting. Drp1-x01 stabilized and bundled microtubules and attenuated staurosporine-induced mitochondrial fragmentation and apoptosis. Phosphorylation of a conserved Ser residue adjacent to the microtubule-binding exon released Drp1-x01 from microtubules and promoted mitochondrial fragmentation in a splice form–specific manner. Phosphorylation by Cdk1 contributed to dissociation of Drp1-x01 from mitotic microtubules, whereas Cdk5-mediated phosphorylation modulated Drp1-x01 targeting to interphase microtubules. Thus, alternative splicing generates a latent, cytoskeletal pool of Drp1 that is selectively mobilized by cyclin-dependent kinase signaling.
6
Mooli, Raja Gopal Reddy, Dhanunjay Mukhi, Zhonghe Chen, Nia Buckner, and Sadeesh K. Ramakrishnan. "An indispensable role for dynamin-related protein 1 in beige and brown adipogenesis." Journal of Cell Science 133, no. 18 (August 25, 2020): jcs247593. http://dx.doi.org/10.1242/jcs.247593.
Full textAbstract:
ABSTRACTEmerging evidence indicates that proper mitochondrial dynamics are critical for adipocyte differentiation and functional thermogenic capacity. We found that the mitochondrial fission protein dynamin-related protein 1 (DRP1, also known as DNML1) is highly expressed in brown adipose tissue compared to expression in white adipose tissue, and these expression levels increase during brown adipocyte differentiation. Our results reveal that the inhibition of DRP1 using mdivi-1 mitigates beige adipocyte differentiation and differentiation-associated mitochondrial biogenesis. We found that DRP1 is essential for the induction of the early-phase beige adipogenic transcriptional program. Intriguingly, inhibition of DRP1 is dispensable following the induction of beige adipogenesis and adipogenesis-associated mitochondrial biogenesis. Altogether, we demonstrate that DRP1 in preadipocytes plays an essential role in beige and brown adipogenesis.This article has an associated First Person interview with the first author of the paper.
7
Cheng, Wen-Yu, Kuan-Chih Chow, Ming-Tsang Chiao, Yi-Chin Yang, and Chiung-Chyi Shen. "Higher Levels of Dynamin-related Protein 1 are Associated with Reduced Radiation Sensitivity of Glioblastoma Cells." Current Neurovascular Research 17, no. 4 (December 14, 2020): 446–63. http://dx.doi.org/10.2174/1567202617666200623123638.
Full textAbstract:
Background: Dynamin-related protein 1 (DRP1) is a GTPase involved in mitochondrial fission, mitochondrial protein import, and drug sensitivity, suggesting an association with cancer progression. This study was conducted to evaluate the prognostic significance of DRP1 in glioblastoma multiforme (GBM). Methods: DRP1 expression was measured by immunohistochemistry and Western blotting. Correlations between DRP1 expression and clinicopathological parameters were determined by statistical analysis. Differences in survival were compared using the log-rank test. DRP1 expression was detected in 87.2% (41/47) of the investigated patients with GBM. Results: The patients with higher DRP1 levels had worse survival (p = 0.0398). In vitro, the silencing of DRP1 reduced cell proliferation, invasive potential, and radiation resistance. The addition of shikonin inhibited DRP1 expression and increased drug uptake. Moreover, shikonin reduced the nuclear entry of DNA repair-associated enzymes and increased radiation sensitivity, suggesting that reducing DRP1 expression could inhibit DNA repair and increase the radiation sensitivity of GBM cells. Conclusion: Our results indicate that DRP1 overexpression is a prospective radio-resistant phenotype in GBM. Therefore, DRP1 could be a potential target for improving the effectiveness of radiation therapy.
8
Bian, Xiyun, Jingman Xu, Huanhuan Zhao, Quan Zheng, Xiaolin Xiao, Xiaofang Ma, Yanxia Li, Xinping Du, and Xiaozhi Liu. "Zinc-Induced SUMOylation of Dynamin-Related Protein 1 Protects the Heart against Ischemia-Reperfusion Injury." Oxidative Medicine and Cellular Longevity 2019 (July 22, 2019): 1–11. http://dx.doi.org/10.1155/2019/1232146.
Full textAbstract:
Background. Zinc plays a role in mitophagy and protects cardiomyocytes from ischemia/reperfusion injury. This study is aimed at investigating whether SUMOylation of Drp1 is involved in the protection of zinc ion on cardiac I/R injury. Methods. Mouse hearts were subjected to 30 minutes of regional ischemia followed by 2 hours of reperfusion (ischemia/reoxygenation (I/R)). Infarct size and apoptosis were assessed. HL-1 cells were subjected to 24 hours of hypoxia and 6 hours of reoxygenation (hypoxia/reoxygenation (H/R)). Zinc was given 5 min before reperfusion for 30 min. SENP2 overexpression plasmid (Flag-SENP2), Drp1 mutation plasmid (Myc-Drp1 4KR), and SUMO1 siRNA were transfected into HL-1 cells for 48 h before hypoxia. Effects of zinc on SUMO family members were analyzed by Western blotting. SUMOylation of Drp1, apoptosis and the collapse of mitochondrial membrane potential (ΔΨm), and mitophagy were evaluated. Results. Compared with the control, SUMO1 modification level of proteins in the H/R decreased, while this effect was reversed by zinc. In the setting of H/R, zinc attenuated myocardial apoptosis, which was reversed by SUMO1 siRNA. Similar effects were observed in SUMO1 KO mice exposed to H/R. In addition, the dynamin-related protein 1 (Drp1) is a target protein of SUMO1. The SUMOylation of Drp1 induced by zinc regulated mitophagy and contributed to the protective effect of zinc on H/R injury. Conclusions. SUMOylation of Drp1 played an essential role in zinc-induced cardio protection against I/R injury. Our findings provide a promising therapeutic approach for acute myocardial I/R injury.
9
Tanner, Michael J., Jingli Wang, Rong Ying, Tisha B. Suboc, Mobin Malik, Allison Couillard, Amberly Branum, Venkata Puppala, and Michael E. Widlansky. "Dynamin-related protein 1 mediates low glucose-induced endothelial dysfunction in human arterioles." American Journal of Physiology-Heart and Circulatory Physiology 312, no. 3 (March 1, 2017): H515—H527. http://dx.doi.org/10.1152/ajpheart.00499.2016.
Full textAbstract:
Intensive glycemic regulation has resulted in an increased incidence of hypoglycemia. Hypoglycemic burden correlates with adverse cardiovascular complications and contributes acutely and chronically to endothelial dysfunction. Prior data indicate that mitochondrial dysfunction contributes to hypoglycemia-induced endothelial dysfunction, but the mechanisms behind this linkage remain unknown. We attempt to determine whether clinically relevant low-glucose (LG) exposures acutely induce endothelial dysfunction through activation of the mitochondrial fission process. Characterization of mitochondrial morphology was carried out in cultured endothelial cells by using confocal microscopy. Isolated human arterioles were used to explore the effect LG-induced mitochondrial fission has on the formation of detrimental reactive oxygen species (ROS), bioavailability of nitric oxide (NO), and endothelial-dependent vascular relaxation. Fluorescence microscopy was employed to visualize changes in mitochondrial ROS and NO levels and videomicroscopy applied to measure vasodilation response. Pharmacological disruption of the profission protein Drp1 with Mdivi-1 during LG exposure reduced mitochondrial fragmentation among vascular endothelial cells (LG: 0.469; LG+Mdivi-1: 0.276; P = 0.003), prevented formation of vascular ROS (LG: 2.036; LG+Mdivi-1: 1.774; P = 0.005), increased the presence of NO (LG: 1.352; LG+Mdivi-1: 1.502; P = 0.048), and improved vascular dilation response to acetylcholine (LG: 31.6%; LG+Mdivi-1; 78.5% at maximum dose; P < 0.001). Additionally, decreased expression of Drp1 via siRNA knockdown during LG conditions also improved vascular relaxation. Exposure to LG imparts endothelial dysfunction coupled with altered mitochondrial phenotypes among isolated human arterioles. Disruption of Drp1 and subsequent mitochondrial fragmentation events prevents impaired vascular dilation, restores mitochondrial phenotype, and implicates mitochondrial fission as a primary mediator of LG-induced endothelial dysfunction. NEW & NOTEWORTHY Acute low-glucose exposure induces mitochondrial fragmentation in endothelial cells via Drp1 and is associated with impaired endothelial function in human arterioles. Targeting of Drp1 prevents fragmentation, improves vasofunction, and may provide a therapeutic target for improving cardiovascular complications among diabetics. Listen to this article’s corresponding podcast @ http://ajpheart.podbean.com/e/mitochondrial-dynamics-impact-endothelial-function/ .
10
Yu, Rong, Tong Liu, Chenfei Ning, Fei Tan, Shao-Bo Jin, Urban Lendahl, Jian Zhao, and Monica Nistér. "The phosphorylation status of Ser-637 in dynamin-related protein 1 (Drp1) does not determine Drp1 recruitment to mitochondria." Journal of Biological Chemistry 294, no. 46 (September 18, 2019): 17262–77. http://dx.doi.org/10.1074/jbc.ra119.008202.
Full textAbstract:
Recruitment of the GTPase dynamin-related protein 1 (Drp1) to mitochondria is a central step required for mitochondrial fission. Reversible Drp1 phosphorylation has been implicated in the regulation of this process, but whether Drp1 phosphorylation at Ser-637 determines its subcellular localization and fission activity remains to be fully elucidated. Here, using HEK 293T cells and immunofluorescence, immunoblotting, RNAi, subcellular fractionation, co-immunoprecipitation assays, and CRISPR/Cas9 genome editing, we show that Drp1 phosphorylated at Ser-637 (Drp1pS637) resides both in the cytosol and on mitochondria. We found that the receptors mitochondrial fission factor (Mff) and mitochondrial elongation factor 1/2 (MIEF1/2) interact with and recruit Drp1pS637 to mitochondria and that elevated Mff or MIEF levels promote Drp1pS637 accumulation on mitochondria. We also noted that protein kinase A (PKA), which mediates phosphorylation of Drp1 on Ser-637, is partially present on mitochondria and interacts with both MIEFs and Mff. PKA knockdown did not affect the Drp1-Mff interaction, but slightly enhanced the interaction between Drp1 and MIEFs. In Drp1-deficient HEK 293T cells, both phosphomimetic Drp1-S637D and phospho-deficient Drp1-S637A variants, like wild-type Drp1, located to the cytosol and to mitochondria and rescued a Drp1 deficiency-induced mitochondrial hyperfusion phenotype. However, Drp1-S637D was less efficient than Drp1-WT and Drp1-S637A in inducing mitochondrial fission. In conclusion, the Ser-637 phosphorylation status in Drp1 is not a determinant that controls Drp1 recruitment to mitochondria.
Dissertations / Theses on the topic "Dynamin Related Protein 1 (Drp1)"
1
Dickey, Audrey Sarah. "Role of pp2a/bβ2 and pka/akap1 in brain development and function via dynamin-related protein 1 (drp1) control of mitochondria shape and bioenergetics." Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/3444.
Full textAbstract:
Mitochondria are critical for energy production and Ca2+ homeostasis and undergo fission and fusion reactions, perturbation of which can contribute to neuronal injury and disease. Mitochondrial fission is catalyzed by Drp1 (dynamin-related protein 1), a large GTPase tightly controlled by various posttranslational modifications, including phosphorylation. Bβ2 is a neuron-specific postnatally induced protein phosphatase 2A (PP2A) regulatory subunit that mediates PP2A translocation to the outer mitochondrial membrane (OMM) to promote mitochondrial fragmentation and sensitize neurons to various injuries. Opposing PP2A/Bβ2's effect on mitochondrial morphology and cell death is protein kinase A (PKA) anchored to the OMM via A kinase anchoring protein 1 (AKAP1). This dissertation describes how reversible phosphorylation of Drp1 at a conserved Serine residue by an outer mitochondrial kinase (PKA/AKAP1) and phosphatase complex (PP2A/Bβ2) affects dendrite and synapse development in hippocampal neurons and synaptic plasticity and learning and memory in vivo.
Inducing mitochondria fragmentation decreases dendritic arbor complexity, but increases spine and synapse number. Mitochondrial elongation induces opposite effects. L-carnitine increases mitochondria membrane potential and recapitulates the dendritic and synaptic effects of mitochondrial elongation. Epistasis experiments substantiate our hypothesis that PP2A/Bβ2 dephosphorylates and PKA/AKAP1 phosphorylates Drp1 to change mitochondrial shape and regulate mitochondria localization, dendrite outgrowth, and synapse development.
Bβ2 null mice are viable and fertile, without obvious abnormalities. Bβ2 null mice demonstrate significantly larger cortical and hippocampal neuronal mitochondria than in wildtype. Bβ2 deletion decreases spine number on apical and basal cortical dendrites and hippocampal dendrites. Bβ2 null mice display significantly decreased input/output relationship in the hippocampus, consistent with a decrease in synapse number. In a combined context and cued fear-conditioning protocol, the hippocampal-dependent context recall trial revealed significant deficits in Bβ2 null and heterozygous mice. This deficit is also seen in hippocampal-dependent Barnes maze performance. These results are consistent with the reduced hippocampal long-term potentiation (LTP) found in Bβ2 null mice and demonstrate the importance of Bβ2 in hippocampal synaptic plasticity and memory. In conclusion, PP2A/Bβ2 and PKA/AKAP1 have important roles in mitochondria regulation and dendritic and synaptic development as seen in our results in vitro with rat hippocampal cultures and in vivo with Bβ2 null mice.
2
Grohm, Julia [Verfasser], and Carsten [Akademischer Betreuer] Culmsee. "Molecular regulation of mitochondrial dynamics by dynamin-related protein 1 (Drp1) and Bid in model systems of neuronal cell death / Julia Grohm. Betreuer: Carsten Culmsee." Marburg : Philipps-Universität Marburg, 2011. http://d-nb.info/1013288408/34.
Full text
3
Harder, Zdena. "The mechanism of mitochondrial fission: Dynamin-related protein 1 and its effectors." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26650.
Full textAbstract:
Mitochondrial fission requires the evolutionarily conserved dynamin related GTPase (DRP1), which is recruited from the cytosol to the mitochondrial outer membrane (1--3) to co-ordinate membrane scission (see (4) for review). Currently, the mechanism of recruitment and assembly of DRP1 on the mitochondria is unclear. Here, using yeast two-hybrid, we identify Ubc9 and SUMO1 as novel DRP1 interacting proteins. We have determined that the interaction between DRP1 and SUMO1 requires SUMO1 conjugation and is nucleotide dependent. Pull-down experiments reveal that DRP1 is an authentic SUMO1 substrate and is likely modified by more than one SUMO1 molecule. Biochemical fractionation indicates that purified mitochondrial fractions contain a NEM-sensitive, SDS-resistant high molecular weight form of DRP1, consistent with the size of SUMOylated DRP1. Importantly, fluorescence microscopy reveals that a significant portion of cytosolic YFP:SUMO1 colocalizes with mitochondria. Video analysis further demonstrates that YFP:SUMO1 is often found at the site of mitochondrial fission and remains tightly associated to the tips of fragmented mitochondria. Surprisingly, immunofluorescence studies show that endogenous DR-P1 only partially colocalizes with the many YFP: SUMO1 puncta seen on the mitochondria, suggesting that mitochondria contain other SUMOylated substrates. This is consistent with the presence of numerous unique SUMOylated products in the mitochondrial fraction. Finally, transient transfection of SUMO1 into cultured cells dramatically increases the level of mitochondrial fragmentation and protects DRP1 from protein degradation. Together, these data are the first to identify a function for SUMO1 on the mitochondria and suggest a novel role for the participation of SUMO1 in mitochondrial fission.
4
Bagheri, Mehran. "Intrinsically Disordered Proteins: Mechanics, Assemblies, and Structural Transitions." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36576.
Full textAbstract:
Proteins are essential parts of living organisms that initiate and control almost all cellular processes. Despite the widely accepted belief that all functional proteins fold into stable and well-defined three-dimensional (3D) structures mandatory for protein activity, the existence of biologically functional disordered proteins has been increasingly recognized during past two decades. Proteins with inherent structural disorder, commonly known as intrinsically disordered proteins (IDPs), play many roles in a biological context. However, in contrast to their folded counterparts, they are dynamically unstructured and typically fluctuate among many conformations even while performing biological functions. In fact, it is this dynamical structural heterogeneity that that allows for IDPs to interact with other biological macromolecules in unique ways. Moreover, while a majority of proteins in eukaryotic proteomes have been found to have intrinsically disordered regions (IDR), the mechanisms by which protein disorder fives rise to biological functionality is still not well understood. Through a series of simulation studies on specific systems, this thesis probes several aspects of the emerging structure-function paradygm of IDPs, namely the mechanics, intermolecular assembly, and structural transitions occurring in these proteins. The lack of well-defined 3D structure in IDPs gives rise to distinct mechanical properties, the subject of the first study in the thesis on the elasticity of a elastomeric gluten-mimetic polypeptide with an intrinsically disordered character. This disordered polypeptide was shown to exhibit distinctively variable elastic response to a wide range of tensions, which a classical worm-like chain model failed to accurately describe, thus requiring a molecular-level analysis. IDPs frequently are frequently involved in protein-protein interactions, the focus of the second study on the propensity of an IDR, the B domain in dynamin-related protein 1 (Dpr1), to self-assemble into dimer structures while remaining disordered in all solution conditions. Despite a hypothesized auto-inhibitory role for this domain in Dpr1 that was assumed to be triggered by an disordered-to-order transition, the B domains in solution showed no tendency to form ordered structures even in the presence of order promoting osmolytes. Instead, self-association in the presence of osmolyte was found to occur by favorable intermolecular intereactions between specific region on the surface of the B-domains. Other IDPs do undergo a disorder-to-order transition in response to environmental cues, in ways that are unique disordered proteins, the focus of the last study on intermolecular ordering transitions in silk-like proteins. Factors such as protein sequence and physical tension were investigated, and results suggested that tyrosine residues in the key silk sequence motifs promote templating of beta structure from disordered precursors and that elongational stresses preferentialy stabilize antiparallel beta-sheet order. Together, these three computational studies provide insight into the nature of the structure-function mechanisms of IDPs.
5
Slupe, Andrew Michael. "Regulation of dynamin-related protein 1-mediated mitochondrial fission by reversible phosphorylation and its contribution to neuronal survival following injury." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4756.
Full textAbstract:
Mitochondria are dynamic organelles that constantly undergo opposing fission and fusion events which impact many aspects of mitochondrial and cellular homeostasis including bioenergetic activity, calcium buffering and organelle transport. The large GTPase dynamin-related protein 1 (Drp1) acts as a mechanoenzyme to catalyze fission of mitochondria. Drp1 activity is regulated through a series of reversible posttranslational modifications. Phosphorylation of the conserved serine residue, S656, by cAMP dependent protein kinase A (PKA) acts as a master regulator of Drp1 activity. Two phosphatases oppose PKA by dephosporylating Drp1 S656, a mitochondrial isoform of protein phosphatase 2A and the calcium-calmodulin dependent phosphatase calcineurin (CaN). Here I report the characterization of a conserved CaN docking site on Drp1, an LxVP motif, just upstream of the Drp1 S656 site. Mutational modification of the Drp1 LxVP motif resulted in selective bidirectional modulation of formation of the CaN:Drp1 complex. Stability of the CaN:Drp1 LxVP motif mutant complexes was qualitatively described by affinity purification and quantitatively described by isothermal titration calorimetry. Stability of the CaN:Drp1 complex was found to directly correlate with Drp1 S656 dephosphorylation kinetics as demonstrated by studies conducted in vitro and in intact cells. Further, the CaN:Drp1 signaling axis was shown to shape basal mitochondrial morphology in a heterologous cell line system and in primary hippocampal neurons. Finally, disruption of the CaN:Drp1 signaling axis was found to protect neurons from oxygen-glucose deprivation, an in vitro model of ischemic injury. While these results suggest that the CaN:Drp1 signaling axis may be a potential target for neuroprotective therapeutic exploitation, the mechanism by which disruption of the CaN:Drp1 signaling axis specifically and mitochondrial elongation generally results in resistance to ischemic injury remains unknown.
Additional studies reported here demonstrate that mitochondrial fragmentation remains a prominent feature of injured neurons regardless of the fidelity of the CaN:Drp1 signaling axis. Mitochondrial fragmentation at the time of injury was found to occur in a Drp1-independent manner. Chronic mitochondrial elongation was also found to leave unaltered the ability of neurons to detoxify reactive oxygen species, buffer intracellular calcium and supply ATP for homeostatic function.
6
Cellier, Laura. "Rôle de la dynamique mitochondriale à la phase aiguͭe de l'infarctus du myocarde Increase in Cardiac Ischemia-Reperfusion Injuries in Opa1+/- Mouse Model Remote ischemic conditioning influences mitochondrial dynamics." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0085.
Full textAbstract:
L’infarctus du myocarde (IDM) est une pathologie décrite comme étant "la mort des cellules myocardiques après une ischémie prolongée". Actuellement, la reperfusion est la stratégie la plus efficace pour limiter l’étendue de cette nécrose myocardique et améliorer le pronostic des patients. Cependant, cette reperfusion entraine des lésions secondaires irréversibles que l’on appelle lésions de reperfusion. Pour protéger le coeur de ces lésions de reperfusion, des stratégies sont à l’étude avec notamment la cardioprotection par le conditionnement ischémique à distance. Ce conditionnement consiste à réaliser de courts épisodes d'ischémie-reperfusion (IR) non délétères au niveau d’un organe distant du coeur. La mitochondrie est un acteur central dans la genèse des lésions de reperfusion mais aussi dans les mécanismes de cardioprotection. Plusieurs études suggèrent que la modulation de la dynamique mitochondriale, regroupant les mécanismes de fission-fusion mitochondriale, pourrait être une nouvelles tratégie thérapeutique pour diminuer les lésions de reperfusion. Dans ce travail nous avons étudié deux modèles de souris transgéniques déficientes soit en protéine de fusion Optic Atrophy 1 (OPA1), soit en protéine de fission Dynamin Related Protein 1 (DRP1). Nous avons montré qu’un déficit partiel en OPA1 était associé à une augmentation des lésions d’IR et à un déséquilibre dans les flux calciques mitochondriaux alors qu’un déficit partiel en DRP1 réduisait les lésions d’IR. Ces données suggèrent qu’une stratégie thérapeutique ciblant la dynamique mitochondriale en faveur d’une fusion pourrait diminuer les lésions d’IRMyocardial infarction (MI) is defined in pathology as « myocardial cell death due to prolonge dischemia ». Currently, reperfusion is the most effective strategy to limit the extent of this myocardial necrosis and to improve the prognosis of patients. Paradoxically, this reperfusion is the cause of additional irreversible damage, called reperfusion injuries. A strategy that was proven efficient in reducing these injuries is the remote ischemic conditioning (RIC). This strategy consists of applying brief, non invasive, episodes of ischemia reperfusion (IR) to an organ or a tissue distant from the ischemic organ, here the heart. Mitochondria play amajor role in both reperfusion injuries and cardioprotection mechanisms. Several studies suggest that the modulation of mitochondrial dynamics, which is mitochondrial fission and fusion mechanisms, could be a new therapeutic strategy for reducing reperfusion injuries. In this work, we studied two transgenic mouse models, one model is deficient in Optic Atrophy 1(OPA1) fusion protein and the other one is deficient in Dynamin Related Protein 1 (DRP1) fission protein. We showed that a partial OPA1 deficiency was associated with an increase in IR injuries and an imbalance in mitochondrial calcium flux, whereas, a partial DRP1 deficiency decreased IR injuries. These data suggest that a therapeutic strategy modulating the mitochondrial dynamics in favor of fusion could reduce IR injuries
7
Lin, Ruen-Chi, and 林潤琪. "GSK3β Interacts with and Phosphorylates Drp1 (Dynamin related protein 1 )/HdynIV (Human dynamin IV) that Affects Mitochondrial Morphology." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/95670546959807308919.
Full textAbstract:
碩士高雄醫學大學
生物化學研究所
98
GSK3 (Glycogen Synthase Kinase) belongs to Serine/Theronine kinase family, with multifunction in many vital pathways. Posttranslational modification of dynamin related protein 1 (Drp1/HdynIV) emerged as regulatory mechanisms affecting various activities during mitochondrial fission. Recent study has demonstrated that S-nitrosylation of Drp1/HdynIV triggered mitochondrial fission in Alzheimer''s disease. However, the phosphorylation of Drp1/HdynIV function remains unclear. In our previous studies, we have demonstrated that Drp1/HdynIV and its splicing variants interact with the GSK3β through their carboxyl-terminal lack of proline-rich domain region. In this report, we further narrow down the binding region locates at 634-690 region in Drp1/HdynIV GTPase effector domain. We also perform in vitro kinase assays to examine whether Drp1/HdynIV is a physiological substrate for GSK3β . The data show that fragments of 691-736 a.a (Drp1/HdynIV) is phosphorylated. It is noted that 691-736 a.a of Drp1/HdynIV does not contain binding site, suggesting that binding site is not required for phosphorylation. Further, in vivo assay show that wild type and S693A were transfected into HeLa cells to assess mitochondria morphology, Intriguingly, the data indicate that phosphorylation at GED domain of Ser 693 Drp1/HdynIV results in the alterations of mitochondrial morphology which likely involved in dynamic regulation of mitochondrial division in cells. In summary, we propose that in addition to Drp1/HdynIV nitrosylation, phosphorylation of Drp1/HdynIV by GSK3β may be thought to be another key mediator of Drp1/HdynIV activity.
8
Liao, Huei De, and 廖惠德. "GSK3β-mediated Phosphorylation of Drp1(Dynamin-related protein 1)HdynIV(Human dynamin IV)Ser693 influences its GTPase activity and Mitochondria dynamics." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/43699139141853939685.
Full textAbstract:
碩士高雄醫學大學
生物化學研究所
99
Mitochondria dynamics is involved in its’ intracellular distribution which is associated with neurondegeneration. Study indicates that mutant of Drp1 may cause mitochondrial distribution change. Some cells, such as brain cells, strongly rely on the mitochondria to generate energy in specific location at appropriate time. In addition, mitochondria dynamics is greatly shifted toward fission in Alzheimer’s disease, one of the neurondegeneration diseases, and mitochondrial fission is associated with G proteins, such as Drp1. Drp1 is regulated by different kinase, and GSK3β, one of the regulators of Drp1 plays an important role in neurongenesis. Our lab previously demonstrated that Drp1/Human dynamin IV (HdynIV) interacts with the GSK3β via its carboxyl-terminal region; suggest that Drp1/HdynIV may have correlation closely with cell signaling. Moreover, we found that Drp1/HdynIV Ser693 is phosphorylated by GSK3β and the mutant Ser693Ala of Drp1 lost most of the phosphorylation, which further confirm by S693D mutant. Drp1 interacts with its receptor hFIS1 for oligomerization and the GTPase activity is crucial for mitochondrial fission. Thus, we want to find out whether Drp1 S693 mutants reduce their GTPase activity in order to affect mitochondria dynamics. Yeast two hybrid indicated that S693A and S693D didn’t affect the intra-interaction of Drp1, but GTPase activity decreased, which was detected by GTPase coupled enzyme assay. We observed mitchondria morphology in Hela cells tranfected with Drp1 wild type and mutants. The statistic showed that S693D strong;y affected mitochondria morphology and S693A is differed from wild type. These results suggest that Ser693 site might play a role in Drp1 function and mitchochondria dynamics, which may become a drug target for neurondegeneration disease.
9
Fonseca, Tiago Alexandre Branco. "The role of dynamins and dynamin-related protein 1 (Drp 1) in the regulation of mitochondrial and peroxisomal fission." Master's thesis, 2017. http://hdl.handle.net/10316/82986.
Full textAbstract:
Dissertação de Mestrado em Biologia Celular e Molecular apresentada à Faculdade de Ciências e TecnologiaPeroxisomas e mitocôndrias são organelos extremamente dinâmicos presentes em quase todas as células. As mitocôndrias, fábricas energéticas, apresentam ciclos contínuos de fusão e fissão que constantemente influenciam e adaptam o retículo mitocondrial às necessidades das células. Por outro lado, peroxisomas conseguem proliferar continuamente através de processos de divisão, mas também são capazes de ser formados a partir de outros compartimentos celulares. Em ambos os casos, estes processos dinâmicos são regulados por proteínas capazes de remodelarem membranas, algumas das quais são mesmo partilhadas entre estes dois organelos, nomeadamente a Dynamin-related protein 1 (Drp1), uma proteína que pertence à superfamília das dinaminas. Quando recrutada, a Drp1 forma estruturas em hélice em torno das membranas de um peroxisoma ou de uma mitocôndria para completar a separação das suas membranas. Contudo, foi recentemente sugerido que o diâmetro destas hélices da Drp1 parece não proporcionar a energia necessária para a divisão das mitocôndrias e que a Dinamina 2 (Dyn 2), também da superfamília das dinaminas, seria capaz de resolver esta limitação da Drp1, provocando a clivagem final das membranas durante a sua divisão. No entanto, este mecanismo ainda não foi estudado para a fissão dos peroxisomas.Dado que a Dyn2 e outras duas isoformas (Dyn1/2/3) constituem as dinaminas clássicas, nós decidimos usar um modelo condicional para eliminar todas estas isoformas de forma a estudar o seu papel na fissão dos peroxisomas e em mais detalhe na divisão mitocondrial. Os nossos resultados mostram que a morfologia dos peroxisomas não depende destas proteínas. Além disso, a eliminação das três isoformas não resulta na elongação das mitocôndrias, ao contrário do que acontece com a inibição da Drp1. Por outro lado, através de live-cell imaging observámos diversos estímulos que induziram a fragmentação mitocondrial independentemente das Dyn1/2/3. Contudo, é importante realçar que a funcionalidade da mitocôndria poderá estar alterada neste modelo de triple knockout das Dyn1/2/3.Os nossos resultados revelam a complexidades de ambos os processos de divisão e ajudam a compreender mais a regulação dos mesmos, mostrando que provavelmente as Dyn1/2/3 são dispensáveis tanto para a divisão dos peroxisomas como para a divisão mitocondrial em resposta a certos estímulos ou em condições basais.
Peroxisomes and mitochondria are extremely dynamic organelles. Mitochondria, the cellular powerhouse, present ongoing cycles of fusion and fission that constantly influence and reshape the mitochondrial reticulum. Peroxisomes, in turn, proliferate through growth and division processes, being also capable of arising from different cellular compartments. These dynamic processes are regulated by membrane-remodelling proteins, some of which are shared between the two organelles, such as Dynamin-related protein 1 (Drp1), a member of the superfamily of dynamin proteins. Drp1 is recruited and assembled in helical rings around peroxisomes or mitochondria undergoing division to fully separate their membranes. However, the diameter of Drp1 rings has been suggested to not provide the necessary constricting force in mitochondrial fission. Recently, Dynamin 2 (Dyn 2), another member of this family, seems to assume the final cleavage step in Drp1-mediated mitochondrial division, thereby resolving this conundrum in Drp1 fission. Whether this mutual Drp1-Dyn2 division is involved in peroxisome division is unknown. Since Dyn2 is one of the three classical dynamins (Dyn1/2/3) expressed in mammalian cells, we decided to use a conditional-triple knockout model of these three dynamins to investigate their role in peroxisome division and mitochondrial division. Our results suggest that peroxisome morphology is unaltered regardless of Dyn1/2/3 deletion. Moreover, depletion of Dyn1/2/3 did not result in mitochondrial elongation, whereas knockdown of Drp1 induced the formation of a hyperfused mitochondrial network. Furthermore, in live-cell imaging of calcium- and depolarisation-induced fragmentation of mitochondria, Dyn1/2/3-depleted cells did not reveal a division blockage. However, mitochondrial metabolism in this triple knockout model is altered. Our results shed light on the complexity of mitochondrial and peroxisomal fission and help understand in more detail how peroxisome and mitochondrial fission are regulated, suggesting that Dyn1/2/3 are not involved in peroxisomal fission and that certain stimuli might not require Dyn2 and/or that Dyn2 is not absolutely needed for mitochondrial fission.
Outro - European Research Council grant received by Doctor Nuno Raimundo.
10
Prasanna, Katti. "Investigating the Novel Roles of miR-9a and the Regulators of Mitochondrial Dynamics During the Development and Functioning of Indirect Flight Muscles in Drosophila melanogaster." Thesis, 2016. http://etd.iisc.ac.in/handle/2005/4330.
Full textAbstract:
The muscular system is a highly complex and important system in the body. Proper muscle physiology is critical for locomotion, digestion, circulation, reproduction as well as for metabolic and immune homeostasis. Defects in muscle development, structure or function result in muscle disorders and diseases. Chapter 1 reviews the important events of muscle development and growth as well as the various processes that are involved in the regulation of the same. The muscle disorders that occur due to the mis -regulation of these processes are discussed. Specifically, the significance of microRNAs in muscle development and function in the context of cardiac hypertrophy has been described. Chapter 1 also explains the importance of mitochondrial morphology and function for normal tissue functioning along with the dynamic processes that mediate changes in mitochondrial shape and size, namely fusion and fission. Thus, the first chapter discusses what is known and unknown about the roles played by microRNAs in and the regulators of mitochondrial dynamics during muscle development, and highlights questions being addressed in the present thesis. The advantages of using the Drosophila indirect flight muscle (IFMs) as a model system to address the unanswered questions are also enumerated in this chapter. The main features of IFM development and the similarities with vertebrate muscle development have been highlighted.
Chapter 2 details the various Drosophila melanogaster lines, genetic tools and the experimental techniques used in this study. In the context of muscle function, the spatial and temporal regulation of the expression and assembly of structural proteins into structural units (sarcomeres) is crucial. The derailing of this process has been shown to result in number of muscle defects. One among them is cardiac hypertrophy which is characterized by mis-regulation of structural protein levels. Recently, miR-9 was shown to be involved in cardiac hypertrophy, however the role played by miR-9 in the regulation of muscle proteins is not known.
Chapter 3 explains the novel findings regarding the role of miR-9a (Drosophila homolog) in the regulation IFM development. Results from IFM-specific over-expression of miR-9a during early muscle development indicate that miR-9a may have a role in repressing the regulators of dorsal longitudinal muscles (DLMs – a subset of the IFMs) patterning. The results discussed in this chapter also reveal that the over-expression of miR-9a exclusively in the IFMs during myofibrillogenesis rendered the flies flightless and the muscles showed hypercontraction -an auto-destructive process resulting from mis-regulated acto-myosin interactions. Bioinformatics analysis predicted 27 putative targets of miR-9a in muscles and Troponin-T (TnT), a structural protein component of the thin filament complex required for regulation of muscle contraction, was identified as putative target of miR-9a . Based on the observations that TnT levels are reduced when miR-9a is over-expressed and that overexpression of TnT, which lacked the miR-9a binding site, resulted in rescue of miR-9a over-expression phenotype, Chapter 3 concludes by stating that Troponin T is a major target of miR-9a in the IFMs. This finding along with the fact that human cardiac Troponin T (TNNT2) possesses a miR-9 binding site indicates that miR-9 could be involved in regulating the Troponin T levels during cardiac hypertrophy. Maintenance of mitochondrial quality and quantity is vital particularly in an energetically active tissue such as muscle. Mutations in the genes encoding regulators of mitochondrial dynamics have been shown to result in degenerative diseases. However, the process of mitochondrial fusion and fission are not well studied in vivo , especially during tissue development.
In Chapter 4, the changes in mitochondrial morphology across IFM development have been described for the first time. Since all the major events of myogenesis during IFM development have been well demarcated and can be spatio-temporally tracked, it serves as a good model to investigate the mitochondria dynamics and roles of molecular players. Mitochondrial morphology was observed to be thin and continuous in the early stages of development, circular during mid-pupal phase and large and tubular during late pupal stage, indicating the occurrence of both mitochondrial fusion and fission during myogenesis. Further, Chapter 4 details the effect of knock down of the regulators of mitochondrial fusion and fission, namely Mitochondrial associated regulatory factor (Marf) and Dynamin related protein 1 (Drp1) during development of the IFMs. Genetic studies that revealed the importance of these regulators in mammalian development and human diseases are also mentioned. The results presented in Chapter 4 show that the knock down of
Marf during development of the IFMs resulted in abnormal mitochondrial morphology and dysfunctional mitochondria that undergo mitophagy. While, Marf expression was found to be vital during early in IFM development, it did not appear to be as necessary during later in development. Knock down of Marf during the myofibrillogenesis phase of IFM development did not result in any defect in mitochondrial morphology function and myofibril ultrastructure. Importantly, it is shown in Chapter 4 that when Marf was depleted from early in development, adult flies exhibited abnormal sarcomeric structures, were incapable of flight and had greatly reduced life span. On the other hand, knock down of Drp1, the regulator of fission did not affect the mitochondrial morphology, muscle function and myofibril ultrastructure. Therefore, for the first time, this study reports that the spatiotemporal regulation of mitochondrial fusion and not fission appears to be critical for IFM development, maintenance, and function. In conclusion, the present study offers the following novel insights into the regulation of IFM development and the how specific developmental events influence IFM function; I) The major target of miR-9a in IFMs is Troponin T, whose levels must be regulated during myofibrillogenesis in order to achieve stoichiometric balance essential for muscle contraction. II) The expression of Marf, a mediator of mitochondrial fusion is crucial during a window of time in IFM development in order to achieve normal mitochondria morphology and function as well as structurally sound, functional muscle fibres in adult.
Book chapters on the topic "Dynamin Related Protein 1 (Drp1)"
1
Montecinos-Franjola, Felipe, and Rajesh Ramachandran. "Imaging Dynamin-Related Protein 1 (Drp1)-Mediated Mitochondrial Fission in Living Cells." In Methods in Molecular Biology, 205–17. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0676-6_16.
Full text
2
Montecinos-Franjola, Felipe, and Rajesh Ramachandran. "Correction to: Imaging Dynamin-Related Protein 1 (Drp1)-Mediated Mitochondrial Fission in Living Cells." In Methods in Molecular Biology, C1. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0676-6_17.
Full text
3
Clinton, Ryan W., Brianna L. Bauer, and Jason A. Mears. "Affinity and Functional Characterization of Dynamin-Related Protein 1." In Methods in Molecular Biology, 41–53. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0676-6_4.
Full text
4
Varlakhanova, Natalia V., and Marijn G. J. Ford. "Purification of the Dynamin-Related Protein Using Mammalian and Bacterial Expression Systems." In Methods in Molecular Biology, 17–27. New York, NY: Springer US, 2020. http://dx.doi.org/10.1007/978-1-0716-0676-6_2.
Full text
5
"DRP (dynamin-related protein)." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics, 563. Dordrecht: Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_4900.
Full text
6
Griparic, Lorena, and Alexander M. van der Bliek. "Assay and Properties of the Mitochondrial Dynamin Related Protein Opa1." In Methods in Enzymology, 620–31. Elsevier, 2005. http://dx.doi.org/10.1016/s0076-6879(05)04054-1.
Full text
7
Cribbs, J. Thomas, and Stefan Strack. "Chapter 13 Functional Characterization of Phosphorylation Sites in Dynamin‐Related Protein 1." In Methods in Enzymology, 231–53. Elsevier, 2009. http://dx.doi.org/10.1016/s0076-6879(09)05013-7.
Full textConference papers on the topic "Dynamin Related Protein 1 (Drp1)"
1
Qian, Wei, Vera Roginskaya, Sandra Strychor, Jan Beumer, Lee McDermott, Jingnan Wang, and Bennett Van Houten. "Abstract 946: Mitochondrial division inhibitor 1 (mdivi-1) overcomes cisplatin resistance independent of dynamin-related protein 1 (Drp1)." In Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC. American Association for Cancer Research, 2013. http://dx.doi.org/10.1158/1538-7445.am2013-946.
Full text
2
Abu-Hanna, Jeries, Jan-Willem Taanman, David Abraham, and Lucie Clapp. "Impact of treprostinil on dynamin-related protein 1 (DRP1) and mitochondrial fragmentation in pulmonary arterial hypertension (PAH)." In ERS International Congress 2018 abstracts. European Respiratory Society, 2018. http://dx.doi.org/10.1183/13993003.congress-2018.pa3059.
Full text
3
Wu, D., A. Dasgupta, K. H. Chen, T. Hurst, M. Neuber-Hess, A. Martin, J. Mewburn, et al. "Novel Dynamin-Related Protein 1 GTPase Inhibitor Prevents Myocardial Ischemia-Reperfusion Injury." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2799.
Full text
4
Bruno, S., B. Korwin-Mihavics, A. Kumar, Z. Mark, B. Cunniff, and V. Anathy. "Dynamin Related Protein 1-Mediated Mitochondrial Fission Regulates the Lung Epithelial Response to Allergen." In American Thoracic Society 2019 International Conference, May 17-22, 2019 - Dallas, TX. American Thoracic Society, 2019. http://dx.doi.org/10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a2137.
Full text
5
Zhang, Zhenzhen, Jie Feng, and Shengnan Wu. "Roles of dynamin-related protein 1 in the regulation of mitochondrial fission and apoptosis in response to UV stimuli." In SPIE BiOS, edited by Wei R. Chen. SPIE, 2011. http://dx.doi.org/10.1117/12.874292.
Full textReports on the topic "Dynamin Related Protein 1 (Drp1)"
1
Avni, Adi, and Gitta L. Coaker. Proteomic investigation of a tomato receptor like protein recognizing fungal pathogens. United States Department of Agriculture, January 2015. http://dx.doi.org/10.32747/2015.7600030.bard.
Full textAbstract:
Maximizing food production with minimal negative effects on the environment remains a long-term challenge for sustainable food production. Microbial pathogens cause devastating diseases, minimizing crop losses by controlling plant diseases can contribute significantly to this goal. All plants possess an innate immune system that is activated after recognition of microbial-derived molecules. The fungal protein Eix induces defense responses in tomato and tobacco. Plants recognize Eix through a leucine-rich-repeat receptor- like-protein (LRR-RLP) termed LeEix. Despite the knowledge obtained from studies on tomato, relatively little is known about signaling initiated by RLP-type immune receptors. The focus of this grant proposal is to generate a foundational understanding of how the tomato xylanase receptor LeEix2 signals to confer defense responses. LeEix2 recognition results in pattern triggered immunity (PTI). The grant has two main aims: (1) Isolate the LeEix2 protein complex in an active and resting state; (2) Examine the biological function of the identified proteins in relation to LeEix2 signaling upon perception of the xylanase elicitor Eix. We used two separate approaches to isolate receptor interacting proteins. Transgenic tomato plants expressing LeEix2 fused to the GFP tag were used to identify complex components at a resting and activated state. LeEix2 complexes were purified by mass spectrometry and associated proteins identified by mass spectrometry. We identified novel proteins that interact with LeEix receptor by proteomics analysis. We identified two dynamin related proteins (DRPs), a coiled coil – nucleotide binding site leucine rich repeat (SlNRC4a) protein. In the second approach we used the split ubiquitin yeast two hybrid (Y2H) screen system to identified receptor-like protein kinase At5g24010-like (SlRLK-like) (Solyc01g094920.2.1) as an interactor of LeEIX2. We examined the role of SlNRC4a in plant immunity. Co-immunoprecipitation demonstrates that SlNRC4a is able to associate with different PRRs. Physiological assays with specific elicitors revealed that SlNRC4a generally alters PRR-mediated responses. SlNRC4a overexpression enhances defense responses while silencing SlNRC4 reduces plant immunity. We propose that SlNRC4a acts as a non-canonical positive regulator of immunity mediated by diverse PRRs. Thus, SlNRC4a could link both intracellular and extracellular immune perception. SlDRP2A localizes at the plasma membrane. Overexpression of SlDRP2A increases the sub-population of LeEIX2 inVHAa1 endosomes, and enhances LeEIX2- and FLS2-mediated defense. The effect of SlDRP2A on induction of plant immunity highlights the importance of endomembrane components and endocytosis in signal propagation during plant immune . The interaction of LeEIX2 with SlRLK-like was verified using co- immunoprecipitation and a bimolecular fluorescence complementation assay. The defence responses induced by EIX were markedly reduced when SlRLK-like was over-expressed, and mutation of slrlk-likeusing CRISPR/Cas9 increased EIX- induced ethylene production and SlACSgene expression in tomato. Co-expression of SlRLK-like with different RLPs and RLKs led to their degradation, apparently through an endoplasmic reticulum-associated degradation process. We provided new knowledge and expertise relevant to expression of specific be exploited to enhance immunity in crops enabling the development of novel environmentally friendly disease control strategies.