Journal articles: 'Fission pathways'

1

Cansado, José, Teresa Soto, Alejandro Franco, Jero Vicente-Soler, and Marisa Madrid. "The Fission Yeast Cell Integrity Pathway: A Functional Hub for Cell Survival upon Stress and Beyond." Journal of Fungi 8, no. 1 (December 30, 2021): 32. http://dx.doi.org/10.3390/jof8010032.

Full text

Abstract:

The survival of eukaryotic organisms during environmental changes is largely dependent on the adaptive responses elicited by signal transduction cascades, including those regulated by the Mitogen-Activated Protein Kinase (MAPK) pathways. The Cell Integrity Pathway (CIP), one of the three MAPK pathways found in the simple eukaryote fission of yeast Schizosaccharomyces pombe, shows strong homology with mammalian Extracellular signal-Regulated Kinases (ERKs). Remarkably, studies over the last few decades have gradually positioned the CIP as a multi-faceted pathway that impacts multiple functional aspects of the fission yeast life cycle during unperturbed growth and in response to stress. They include the control of mRNA-stability through RNA binding proteins, regulation of calcium homeostasis, and modulation of cell wall integrity and cytokinesis. Moreover, distinct evidence has disclosed the existence of sophisticated interplay between the CIP and other environmentally regulated pathways, including Stress-Activated MAP Kinase signaling (SAPK) and the Target of Rapamycin (TOR). In this review we present a current overview of the organization and underlying regulatory mechanisms of the CIP in S. pombe, describe its most prominent functions, and discuss possible targets of and roles for this pathway. The evolutionary conservation of CIP signaling in the dimorphic fission yeast S. japonicus will also be addressed.

APA, Harvard, Vancouver, ISO, and other styles

2

Hernáez, M. J., E. Andújar, J. L. Ríos, S. R. Kaschabek, W. Reineke, and E. Santero. "Identification of a Serine Hydrolase Which Cleaves the Alicyclic Ring of Tetralin." Journal of Bacteriology 182, no. 19 (October 1, 2000): 5448–53. http://dx.doi.org/10.1128/jb.182.19.5448-5453.2000.

Full text

Abstract:

ABSTRACT A gene designated thnD, which is required for biodegradation of the organic solvent tetralin by Sphingomonas macrogoltabidus strain TFA, has been identified. Sequence comparison analysis indicated that thnD codes for a carbon-carbon bond serine hydrolase showing highest similarity to hydrolases involved in biodegradation of biphenyl. An insertion mutant defective in ThnD accumulates the ring fission product which results from the extradiol cleavage of the aromatic ring of dihydroxytetralin. The gene product has been purified and characterized. ThnD is an octameric thermostable enzyme with an optimum reaction temperature at 65°C. ThnD efficiently hydrolyzes the ring fission intermediate of the tetralin pathway and also 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid, the ring fission product of the biphenylmeta-cleavage pathway. However, it is not active towards the equivalent intermediates of meta-cleavage pathways of monoaromatic compounds which have small substituents in C-6. When ThnD hydrolyzes the intermediate in the tetralin pathway, it cleaves a C-C bond comprised within the alicyclic ring of tetralin instead of cleaving a linear C-C bond, as all other known hydrolases ofmeta-cleavage pathways do. The significance of this activity of ThnD for the requirement of other activities to mineralize tetralin is discussed.

APA, Harvard, Vancouver, ISO, and other styles

3

Baldacchino, Alexander J., Miles I. Collins, Michael P. Nielsen, Timothy W. Schmidt, Dane R. McCamey, and Murad J. Y. Tayebjee. "Singlet fission photovoltaics: Progress and promising pathways." Chemical Physics Reviews 3, no. 2 (June 2022): 021304. http://dx.doi.org/10.1063/5.0080250.

Full text

Abstract:

Singlet fission is a form of multiple exciton generation, which occurs in organic chromophores when a high-energy singlet exciton separates into two lower energy triplet excitons, each with approximately half the singlet energy. Since this process is spin-allowed, it can proceed on an ultrafast timescale of less than several picoseconds, outcompeting most other loss mechanisms and reaching quantitative yields approaching 200%. Due to this high quantum efficiency, the singlet fission process shows promise as a means of reducing thermalization losses in photovoltaic cells. This would potentially allow for efficiency improvements beyond the thermodynamic limit in a single junction cell. Efforts to incorporate this process into solar photovoltaic cells have spanned a wide range of device structures over the past decade. In this review, we compare and categorize these attempts in order to assess the state of the field and identify the most promising avenues of future research and development.

APA, Harvard, Vancouver, ISO, and other styles

4

Stiefel, Jeffrey, Lili Wang, David A. Kelly, Rozmin T. K. Janoo, Jeffrey Seitz, Simon K. Whitehall, and Charles S. Hoffman. "Suppressors of an Adenylate Cyclase Deletion in the Fission Yeast Schizosaccharomyces pombe." Eukaryotic Cell 3, no. 3 (June 2004): 610–19. http://dx.doi.org/10.1128/ec.3.3.610-619.2004.

Full text

Abstract:

ABSTRACT Schizosaccharomyces pombe utilizes two opposing signaling pathways to sense and respond to its nutritional environment. Glucose detection triggers a cyclic AMP signal to activate protein kinase A (PKA), while glucose or nitrogen starvation activates the Spc1/Sty1 stress-activated protein kinase (SAPK). One process controlled by these pathways is fbp1 + transcription, which is glucose repressed. In this study, we isolated strains carrying mutations that reduce high-level fbp1 + transcription conferred by the loss of adenylate cyclase (git2Δ), including both wis1 − (SAPK kinase) and spc1 − (SAPK) mutants. While characterizing the git2Δ suppressor strains, we found that the git2Δ parental strains are KCl sensitive, though not osmotically sensitive. Of 102 git2Δ suppressor strains, 17 strains display KCl-resistant growth and comprise a single linkage group, carrying mutations in the cgs1 + PKA regulatory subunit gene. Surprisingly, some of these mutants are mostly wild type for mating and stationary-phase viability, unlike the previously characterized cgs1-1 mutant, while showing a significant defect in fbp1-lacZ expression. Thus, certain cgs1 − mutant alleles dramatically affect some PKA-regulated processes while having little effect on others. We demonstrate that the PKA and SAPK pathways regulate both cgs1 + and pka1 + transcription, providing a mechanism for cross talk between these two antagonistically acting pathways and feedback regulation of the PKA pathway. Finally, strains defective in both the PKA and SAPK pathways display transcriptional regulation of cgs1 + and pka1 +, suggesting the presence of a third glucose-responsive signaling pathway.

APA, Harvard, Vancouver, ISO, and other styles

5

Morandini, André C., Sérgio N. Stampar, Alvaro E. Migotto, and Antonio C. Marques. "Hydrocoryne iemanja (Cnidaria), a new species of Hydrozoa with unusual mode of asexual reproduction." Journal of the Marine Biological Association of the United Kingdom 89, no. 1 (February 2009): 67–76. http://dx.doi.org/10.1017/s0025315408002968.

Full text

Abstract:

Hydrocoryne iemanja sp. nov. was found in an aquarium, growing on rhodoliths of coralline algae collected on the south-eastern coast of Brazil (20°40′S 40°2′W). The colonies were reared through maturity in the laboratory. Each colony had up to 7 sessile, long and thin monomorphic zooids, very extensible and flexible, arising from a chitinous, hard dark-brown plate with minute spines. Medusae budded from near the basal part of hydrocaulus, and were released in immature condition, acquiring fully developed interradial gonads 5–7 days after release. Asexual reproduction by longitudinal fission was observed on the hydrocaulus of the polyps, both for those in normal condition and those with injuries. Fission started at the oral region, extending aborally, with a new hard plate formed in the basal part of hydrocaulus. When fission reached the new hard plate, the new polyp detached, becoming free and sinking to the bottom, starting a new colony. Detached polyps were morphologically indistinguishable from other polyps, being able to produce medusae. Mother and daughter polyps undertook subsequent fissions. This mode of longitudinal fission is distinct from other modes of longitudinal fission, a process known for a few species of cnidarians. Further studies of this process may shed light on the understanding of the evolutionary pathways in Cnidaria and animals. Hydrocoryne iemanja sp. nov. is distinguishable from its two congeners by the distinct marginal tentacles of the medusae—short and with a median nematocyst knob—an unambiguous character useful even for the identification of newly liberated medusae.

APA, Harvard, Vancouver, ISO, and other styles

6

Li, Haijun, Fucheng He, Xin Zhao, Yuan Zhang, Xi Chu, Chunlan Hua, Yunhui Qu, Yu Duan, and Liang Ming. "YAP Inhibits the Apoptosis and Migration of Human Rectal Cancer Cells via Suppression of JNK-Drp1-Mitochondrial Fission-HtrA2/Omi Pathways." Cellular Physiology and Biochemistry 44, no. 5 (2017): 2073–89. http://dx.doi.org/10.1159/000485946.

Full text

Abstract:

Background/Aims: The Hippo-Yap pathway is associated with tumor development and progression. However, little evidence is available concerning its role in cancer cell apoptosis and migration via mitochondrial homeostasis. Here, we identify mitochondrial fission as a regulator of the Hippo–Yap pathway in human rectal cancer tumorigenesis and metastasis. Methods: In this study, we performed loss-of function assays concerning Yap in RCC via shRNA. Cellular viability and apoptosis were measured via MTT, the TUNEL assay and trypan blue staining. Mitochondrial function was assessed via JC1 staining, the mPTP opening assay, mitochondrial respiratory function analysis, electron microscopy and immunofluorescence analysis of HtrA2/Omi. Mitophagy and mitochondrial fission were assessed via western blots and immunofluorescence. Cell migration was evaluated via the Transwell assay, wound-healing assay and immunofluorescence analysis of F-actin. The interaction between JNK and Yap was detected via co-immunoprecipitation and Yap recombinant mutagenic plasmid transfection. Western blots were used to analyze signaling pathways in conjunction with JNK inhibitors or HtrA2/Omi siRNA. Results: Yap is upregulated in human rectal cancer cells, where its expression correlates positively with cell survival and migration. Functional studies established that silencing of Yap drove JNK phosphorylation, which induced Drp1 activation and translocation to the surface of mitochondria, initiating mitochondrial fission. Excessive mitochondrial fission mediated HtrA2/Omi leakage from the mitochondria into the cytoplasm, where HtrA2/Omi triggered cellular apoptosis via the mitochondrial apoptosis pathway. Moreover, released HtrA2/Omi also phosphorylated cofilin and inhibited cofilin-mediated F-actin polymerization. F-actin collapse perturbed lamellipodia formation and therefore impaired cellular migration and invasion. Conclusion: Collectively, our results demonstrate that Hippo-Yap can serve as a tumor promoter in human rectal cancer and acts by restricting JNK/Drp1/mitochondrial fission/ HtrA2/Omi, with potential implications for new approaches to human rectal cancer therapy.

APA, Harvard, Vancouver, ISO, and other styles

7

Zhang, Hanwen, Yanshuo Ye, and Wei Li. "Perspectives of Molecular Therapy-Targeted Mitochondrial Fission in Hepatocellular Carcinoma." BioMed Research International 2020 (December 29, 2020): 1–7. http://dx.doi.org/10.1155/2020/1039312.

Full text

Abstract:

Current advances of molecular-targeting therapies for hepatocellular carcinoma (HCC) have improved the overall survival significantly, whereas the results still remain unsatisfied. Recently, much attention has been focused on organelles, such as the mitochondria, to reveal novel strategies to control the cancers. The mitochondria are vital organelles which supply energy and maintain metabolism in most of the eukaryotic cells. They not only execute critical bioenergetic and biosynthetic functions but also regulate ROS homeostasis and apoptosis. Existing in a dynamic equilibrium state, mitochondria constantly undergo the fission and fusion processes in normal situation. Increasing evidences have showed that mitochondrial fission is highly related to the diseases and cancers. Distinctive works have proved the significant effects of mitochondrial fission on HCC behaviors and the crosstalks with other molecular pathways. Here, we provide an overview of the mitochondrial fission and the link with HCC, emphasizing on the underlying molecular pathways and several novel materials that modulate HCC behaviors.

APA, Harvard, Vancouver, ISO, and other styles

8

Hayashi, Yukimasa, Chiaki W. Nakagawa, Norihiro Mutoh, Minoru Isobe, and Toshio Goto. "Two pathways in the biosynthesis of cadystins (γEC)nG in the cell-free system of the fission yeast." Biochemistry and Cell Biology 69, no. 2-3 (February 1, 1991): 115–21. http://dx.doi.org/10.1139/o91-018.

Full text

Abstract:

Small metal-binding peptides, cadystins, with the general structure of (γ-Glu-Cys)n-Gly ((γEC)nG), were synthesized in a cell-free system of fission yeast to examine the in vivo synthetic pathway. The crude enzyme for cadystin synthesis was prepared by ammonium sulfate precipitation (75% saturation) from the 120 000 × g supernatant of the cell extract, and the excess salt in the enzyme fraction was removed by Sephadex gel filtration. Using this crude enzyme fraction, it was shown that there were two pathways for cadystin biosynthesis. One pathway is γ-Glu-Cys (γEC) dipeptidyl transfer from both glutathione (γECG) and cadystins to glutathione and cadystins. The other one is γEC polymerization from (γEC)n and glutathione to (γEC)n+i, followed by glycine addition with glutathione synthetase.Key words: cadystin, fission yeast, cell-free biosynthesis, dipeptidyl transferase.

APA, Harvard, Vancouver, ISO, and other styles

9

Papadakis, Manos A., and Christopher T. Workman. "Oxidative stress response pathways: Fission yeast as archetype." Critical Reviews in Microbiology 41, no. 4 (October 2, 2015): 520–35. http://dx.doi.org/10.3109/1040841x.2013.870968.

Full text

APA, Harvard, Vancouver, ISO, and other styles

10

Xu, Dan-Dan, and Li-Lin Du. "Fission Yeast Autophagy Machinery." Cells 11, no. 7 (March 24, 2022): 1086. http://dx.doi.org/10.3390/cells11071086.

Full text

Abstract:

Autophagy is a conserved process that delivers cytoplasmic components to the vacuole/lysosome. It plays important roles in maintaining cellular homeostasis and conferring stress resistance. In the fission yeast Schizosaccharomyces pombe, autophagy is important for cell survival under nutrient depletion and ER stress conditions. Experimental analyses of fission yeast autophagy machinery in the last 10 years have unveiled both similarities and differences in autophagosome biogenesis mechanisms between fission yeast and other model eukaryotes for autophagy research, in particular, the budding yeast Saccharomyces cerevisiae. More recently, selective autophagy pathways that deliver hydrolytic enzymes, the ER, and mitochondria to the vacuole have been discovered in fission yeast, yielding novel insights into how cargo selectivity can be achieved in autophagy. Here, we review the progress made in understanding the autophagy machinery in fission yeast.

APA, Harvard, Vancouver, ISO, and other styles

11

Duncan, Katelyn M., Donald L. Kellis, Jonathan S. Huff, Matthew S. Barclay, Jeunghoon Lee, Daniel B. Turner, Paul H. Davis, Bernard Yurke, William B. Knowlton, and Ryan D. Pensack. "Symmetry Breaking Charge Transfer in DNA-Templated Perylene Dimer Aggregates." Molecules 27, no. 19 (October 5, 2022): 6612. http://dx.doi.org/10.3390/molecules27196612.

Full text

Abstract:

Molecular aggregates are of interest to a broad range of fields including light harvesting, organic optoelectronics, and nanoscale computing. In molecular aggregates, nonradiative decay pathways may emerge that were not present in the constituent molecules. Such nonradiative decay pathways may include singlet fission, excimer relaxation, and symmetry-breaking charge transfer. Singlet fission, sometimes referred to as excitation multiplication, is of great interest to the fields of energy conversion and quantum information. For example, endothermic singlet fission, which avoids energy loss, has been observed in covalently bound, linear perylene trimers and tetramers. In this work, the electronic structure and excited-state dynamics of dimers of a perylene derivative templated using DNA were investigated. Specifically, DNA Holliday junctions were used to template the aggregation of two perylene molecules covalently linked to a modified uracil nucleobase through an ethynyl group. The perylenes were templated in the form of monomer, transverse dimer, and adjacent dimer configurations. The electronic structure of the perylene monomers and dimers were characterized via steady-state absorption and fluorescence spectroscopy. Initial insights into their excited-state dynamics were gleaned from relative fluorescence intensity measurements, which indicated that a new nonradiative decay pathway emerges in the dimers. Femtosecond visible transient absorption spectroscopy was subsequently used to elucidate the excited-state dynamics. A new excited-state absorption feature grows in on the tens of picosecond timescale in the dimers, which is attributed to the formation of perylene anions and cations resulting from symmetry-breaking charge transfer. Given the close proximity required for symmetry-breaking charge transfer, the results shed promising light on the prospect of singlet fission in DNA-templated molecular aggregates.

APA, Harvard, Vancouver, ISO, and other styles

12

Yao, Pamela J., Uri Manor, Ronald S. Petralia, Rebecca D. Brose, Ryan T. Y. Wu, Carolyn Ott, Ya-Xian Wang, Ari Charnoff, Jennifer Lippincott-Schwartz, and Mark P. Mattson. "Sonic hedgehog pathway activation increases mitochondrial abundance and activity in hippocampal neurons." Molecular Biology of the Cell 28, no. 3 (February 2017): 387–95. http://dx.doi.org/10.1091/mbc.e16-07-0553.

Full text

Abstract:

Mitochondria are essential organelles whose biogenesis, structure, and function are regulated by many signaling pathways. We present evidence that, in hippocampal neurons, activation of the Sonic hedgehog (Shh) signaling pathway affects multiple aspects of mitochondria. Mitochondrial mass was increased significantly in neurons treated with Shh. Using biochemical and fluorescence imaging analyses, we show that Shh signaling activity reduces mitochondrial fission and promotes mitochondrial elongation, at least in part, via suppression of the mitochondrial fission protein dynamin-like GTPase Drp1. Mitochondria from Shh-treated neurons were more electron-dense, as revealed by electron microscopy, and had higher membrane potential and respiratory activity. We further show that Shh protects neurons against a variety of stresses, including the mitochondrial poison rotenone, amyloid β-peptide, hydrogen peroxide, and high levels of glutamate. Collectively our data suggest a link between Shh pathway activity and the physiological properties of mitochondria in hippocampal neurons.

APA, Harvard, Vancouver, ISO, and other styles

13

Gómez-Gil, Elisa, Alejandro Franco, Beatriz Vázquez-Marín, Francisco Prieto-Ruiz, Armando Pérez-Díaz, Jero Vicente-Soler, Marisa Madrid, Teresa Soto, and José Cansado. "Specific Functional Features of the Cell Integrity MAP Kinase Pathway in the Dimorphic Fission Yeast Schizosaccharomyces japonicus." Journal of Fungi 7, no. 6 (June 14, 2021): 482. http://dx.doi.org/10.3390/jof7060482.

Full text

Abstract:

Mitogen activated protein kinase (MAPK) signaling pathways execute essential functions in eukaryotic organisms by transducing extracellular stimuli into adaptive cellular responses. In the fission yeast model Schizosaccharomyces pombe the cell integrity pathway (CIP) and its core effector, MAPK Pmk1, play a key role during regulation of cell integrity, cytokinesis, and ionic homeostasis. Schizosaccharomyces japonicus, another fission yeast species, shows remarkable differences with respect to S. pombe, including a robust yeast to hyphae dimorphism in response to environmental changes. We show that the CIP MAPK module architecture and its upstream regulators, PKC orthologs Pck1 and Pck2, are conserved in both fission yeast species. However, some of S. pombe’s CIP-related functions, such as cytokinetic control and response to glucose availability, are regulated differently in S. japonicus. Moreover, Pck1 and Pck2 antagonistically regulate S. japonicus hyphal differentiation through fine-tuning of Pmk1 activity. Chimeric MAPK-swapping experiments revealed that S. japonicus Pmk1 is fully functional in S. pombe, whereas S. pombe Pmk1 shows a limited ability to execute CIP functions and promote S. japonicus mycelial development. Our findings also suggest that a modified N-lobe domain secondary structure within S. japonicus Pmk1 has a major influence on the CIP signaling features of this evolutionarily diverged fission yeast.

APA, Harvard, Vancouver, ISO, and other styles

14

Zhang, Dan, Renyi Zhang, and David T. Allen. "C–C bond fission pathways of chloroalkenyl alkoxy radicals." Journal of Chemical Physics 118, no. 4 (January 22, 2003): 1794–801. http://dx.doi.org/10.1063/1.1531660.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Peel, Suman, Pauline Macheboeuf, Nicolas Martinelli, and Winfried Weissenhorn. "Divergent pathways lead to ESCRT-III-catalyzed membrane fission." Trends in Biochemical Sciences 36, no. 4 (April 2011): 199–210. http://dx.doi.org/10.1016/j.tibs.2010.09.004.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Bellini, Angela, Pierre-Marie Girard, Ludovic Tessier, Evelyne Sage, and Stefania Francesconi. "Fission Yeast Rad52 Phosphorylation Restrains Error Prone Recombination Pathways." PLoS ONE 9, no. 4 (April 18, 2014): e95788. http://dx.doi.org/10.1371/journal.pone.0095788.

Full text

APA, Harvard, Vancouver, ISO, and other styles

17

Kishimoto, Norihito, and Ichiro Yamashita. "Multiple pathways regulating fission yeast mitosis upon environmental stresses." Yeast 16, no. 7 (May 2000): 597–609. http://dx.doi.org/10.1002/(sici)1097-0061(200005)16:7<597::aid-yea556>3.0.co;2-i.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Taglini, Francesca, Elliott Chapman, Rob van Nues, Emmanuelle Theron, and Elizabeth H. Bayne. "Mkt1 is required for RNAi-mediated silencing and establishment of heterochromatin in fission yeast." Nucleic Acids Research 48, no. 3 (December 11, 2019): 1239–53. http://dx.doi.org/10.1093/nar/gkz1157.

Full text

Abstract:

Abstract Constitutive domains of repressive heterochromatin are maintained within the fission yeast genome through self-reinforcing mechanisms involving histone methylation and small RNAs. Non-coding RNAs generated from heterochromatic regions are processed into small RNAs by the RNA interference pathway, and are subject to silencing through both transcriptional and post-transcriptional mechanisms. While the pathways involved in maintenance of the repressive heterochromatin state are reasonably well understood, less is known about the requirements for its establishment. Here, we describe a novel role for the post-transcriptional regulatory factor Mkt1 in establishment of heterochromatin at pericentromeres in fission yeast. Loss of Mkt1 does not affect maintenance of existing heterochromatin, but does affect its recovery following depletion, as well as de novo establishment of heterochromatin on a mini-chromosome. Pathway dissection revealed that Mkt1 is required for RNAi-mediated post-transcriptional silencing, downstream of small RNA production. Mkt1 physically associates with pericentromeric transcripts, and is additionally required for maintenance of silencing and heterochromatin at centromeres when transcriptional silencing is impaired. Our findings provide new insight into the mechanism of RNAi-mediated post-transcriptional silencing in fission yeast, and unveil an important role for post-transcriptional silencing in establishment of heterochromatin that is dispensable when full transcriptional silencing is imposed.

APA, Harvard, Vancouver, ISO, and other styles

19

Hoffmann, Lena, Marco B. Rust, and Carsten Culmsee. "Actin(g) on mitochondria – a role for cofilin1 in neuronal cell death pathways." Biological Chemistry 400, no. 9 (August 27, 2019): 1089–97. http://dx.doi.org/10.1515/hsz-2019-0120.

Full text

Abstract:

AbstractActin dynamics, the coordinated assembly and disassembly of actin filaments (F-actin), are essential for fundamental cellular processes, including cell shaping and motility, cell division or organelle transport. Recent studies highlighted a novel role for actin dynamics in the regulation of mitochondrial morphology and function, for example, through mitochondrial recruitment of dynamin-related protein 1 (Drp1), a key factor in the mitochondrial fission machinery. Mitochondria are dynamic organelles, and permanent fission and fusion is essential to maintain their function in energy metabolism, calcium homeostasis and regulation of reactive oxygen species (ROS). Here, we summarize recent insights into the emerging role of cofilin1, a key regulator of actin dynamics, for mitochondrial shape and function under physiological conditions and during cellular stress, respectively. This is of peculiar importance in neurons, which are particularly prone to changes in actin regulation and mitochondrial integrity and function. In neurons, cofilin1 may contribute to degenerative processes through formation of cofilin-actin rods, and through enhanced mitochondrial fission, mitochondrial membrane permeabilization, and the release of cytochrome c. Overall, mitochondrial impairment induced by dysfunction of actin-regulating proteins such as cofilin1 emerge as important mechanisms of neuronal death with relevance to acute brain injury and neurodegenerative diseases, such as Parkinson’s or Alzheimer’s disease.

APA, Harvard, Vancouver, ISO, and other styles

20

Maneechote, Chayodom, Siriporn C. Chattipakorn, and Nipon Chattipakorn. "Recent Advances in Mitochondrial Fission/Fusion-Targeted Therapy in Doxorubicin-Induced Cardiotoxicity." Pharmaceutics 15, no. 4 (April 7, 2023): 1182. http://dx.doi.org/10.3390/pharmaceutics15041182.

Full text

Abstract:

Doxorubicin (DOX) has been recognized as one of the most effective chemotherapies and extensively used in the clinical settings of human cancer. However, DOX-mediated cardiotoxicity is known to compromise the clinical effectiveness of chemotherapy, resulting in cardiomyopathy and heart failure. Recently, accumulation of dysfunctional mitochondria via alteration of the mitochondrial fission/fusion dynamic processes has been identified as a potential mechanism underlying DOX cardiotoxicity. DOX-induced excessive fission in conjunction with impaired fusion could severely promote mitochondrial fragmentation and cardiomyocyte death, while modulation of mitochondrial dynamic proteins using either fission inhibitors (e.g., Mdivi-1) or fusion promoters (e.g., M1) can provide cardioprotection against DOX-induced cardiotoxicity. In this review, we focus particularly on the roles of mitochondrial dynamic pathways and the current advanced therapies in mitochondrial dynamics-targeted anti-cardiotoxicity of DOX. This review summarizes all the novel insights into the development of anti-cardiotoxic effects of DOX via the targeting of mitochondrial dynamic pathways, thereby encouraging and guiding future clinical investigations to focus on the potential application of mitochondrial dynamic modulators in the setting of DOX-induced cardiotoxicity.

APA, Harvard, Vancouver, ISO, and other styles

21

Zhang, Peng, Ping Guan, Xiaomiao Ye, Yi Lu, Yanwen Hang, Yanling Su, and Wei Hu. "SOCS6 Promotes Mitochondrial Fission and Cardiomyocyte Apoptosis and Is Negatively Regulated by Quaking-Mediated miR-19b." Oxidative Medicine and Cellular Longevity 2022 (January 27, 2022): 1–19. http://dx.doi.org/10.1155/2022/1121323.

Full text

Abstract:

Background. Mitochondrial dysfunction and abnormal mitochondrial fission have been implicated in the complications associated with I/R injury as cardiomyocytes are abundant in mitochondria. SOCS6 is known to participate in mitochondrial fragmentation, but its exact involvement and the pathways associated are uncertain. Methods and Results. The expression of SOCS6 was analyzed by western blot in cardiomyocytes under a hypoxia and reoxygenation (H/R) model. A dual-luciferase reporter assay was used to confirm the direct interaction between miR-19b and the 3 ′ -UTR of Socs6. In the present study, we found that Socs6 inhibition by RNA interference attenuated H/R-induced mitochondrial fission and apoptosis in cardiomyocytes. A luciferase assay indicated that Socs6 is a direct target of miR-19b. The overexpression of miR-19b decreased mitochondrial fission and apoptosis in vitro. Moreover, the presence of miR-19b reduced the level of SOCS6 and the injury caused by I/R in vivo. There were less apoptotic cells in the myocardium of mice injected with miR-19b. In addition, we found that the RNA-binding protein, Quaking (QK), participates in the regulation of miR-19b expression. Conclusions. Our results indicate that the inhibition of mitochondrial fission through downregulating Socs6 via the QK/miR-19b/Socs6 pathway attenuated the damage sustained by I/R. The QK/miR-19b/Socs6 axis plays a vital role in regulation of mitochondrial fission and cardiomyocyte apoptosis and could form the basis of future research in the development of therapies for the management of cardiac diseases.

APA, Harvard, Vancouver, ISO, and other styles

22

Alao, John-Patrick, Luc Legon, and Charalampos Rallis. "Crosstalk between the mTOR and DNA Damage Response Pathways in Fission Yeast." Cells 10, no. 2 (February 2, 2021): 305. http://dx.doi.org/10.3390/cells10020305.

Full text

Abstract:

Cells have developed response systems to constantly monitor environmental changes and accordingly adjust growth, differentiation, and cellular stress programs. The evolutionarily conserved, nutrient-responsive, mechanistic target of rapamycin signaling (mTOR) pathway coordinates basic anabolic and catabolic cellular processes such as gene transcription, protein translation, autophagy, and metabolism, and is directly implicated in cellular and organismal aging as well as age-related diseases. mTOR mediates these processes in response to a broad range of inputs such as oxygen, amino acids, hormones, and energy levels, as well as stresses, including DNA damage. Here, we briefly summarize data relating to the interplays of the mTOR pathway with DNA damage response pathways in fission yeast, a favorite model in cell biology, and how these interactions shape cell decisions, growth, and cell-cycle progression. We, especially, comment on the roles of caffeine-mediated DNA-damage override. Understanding the biology of nutrient response, DNA damage and related pharmacological treatments can lead to the design of interventions towards improved cellular and organismal fitness, health, and survival.

APA, Harvard, Vancouver, ISO, and other styles

23

Teng, Yong. "Remodeling of Mitochondria in Cancer and Other Diseases." International Journal of Molecular Sciences 24, no. 9 (April 22, 2023): 7693. http://dx.doi.org/10.3390/ijms24097693.

Full text

Abstract:

Mitochondria are highly dynamic and responsive organelles capable of fission and fusion and are a hub of diverse signaling pathways that are fundamental to cellular homeostasis, energy production, metabolism, survival, and death [...]

APA, Harvard, Vancouver, ISO, and other styles

24

Huang, Xinhe, Markos Leggas, and Robert C. Dickson. "Drug Synergy Drives Conserved Pathways to Increase Fission Yeast Lifespan." PLOS ONE 10, no. 3 (March 18, 2015): e0121877. http://dx.doi.org/10.1371/journal.pone.0121877.

Full text

APA, Harvard, Vancouver, ISO, and other styles

25

Bonazzi, Matteo, Stefania Spanò, Gabriele Turacchio, Claudia Cericola, Carmen Valente, Antonino Colanzi, Hee Seok Kweon, et al. "CtBP3/BARS drives membrane fission in dynamin-independent transport pathways." Nature Cell Biology 7, no. 6 (May 8, 2005): 570–80. http://dx.doi.org/10.1038/ncb1260.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Langer, Sidney, M. L. Russell, and Douglas W. Akers. "Fission Product Release Pathways in Three Mile Island Unit 2." Nuclear Technology 87, no. 1 (September 2, 1989): 196–204. http://dx.doi.org/10.13182/nt89-a27647.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Otsubo, Yoko, and Masayuki Yamamoto. "Signaling pathways for fission yeast sexual differentiation at a glance." Journal of Cell Science 125, no. 12 (June 15, 2012): 2789–93. http://dx.doi.org/10.1242/jcs.094771.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Toda, T., S. Dhut, G. Superti-Furga, Y. Gotoh, E. Nishida, R. Sugiura, and T. Kuno. "The fission yeast pmk1+ gene encodes a novel mitogen-activated protein kinase homolog which regulates cell integrity and functions coordinately with the protein kinase C pathway." Molecular and Cellular Biology 16, no. 12 (December 1996): 6752–64. http://dx.doi.org/10.1128/mcb.16.12.6752.

Full text

Abstract:

We have isolated a gene, pmk1+, a third mitogen-activated protein kinase (MAPK) gene homolog from the fission yeast Schizosaccharomyces pombe. The predicted amino acid sequence shows the most homology (63 to 65% identity) to those of budding yeast Saccharomyces Mpk1 and Candida Mkc1. The Pmk1 protein contains phosphorylated tyrosines, and the level of tyrosine phosphorylation was increased in the dsp1 mutant which lacks an attenuating phosphatase for Pmk1. The level of tyrosine phosphorylation appears constant during hypotonic or heat shock treatment. The cells with pmk1 deleted (delta pmk1) are viable but show various defective phenotypes, including cell wall weakness, abnormal cell shape, a cytokinesis defect, and altered sensitivities to cations, such as hypersensitivity to potassium and resistance to sodium. Consistent with a high degree of conservation of amino acid sequence, multicopy plasmids containing the MPK1 gene rescued the defective phenotypes of the delta pmk1 mutant. The frog MAPK gene also suppressed the pmk1 disruptant. The results of genetic analysis indicated that Pmk1 lies on a novel MAPK pathway which does not overlap functionally with the other two MAPK pathways, the Spk1-dependent mating signal pathway and Sty1/Spc1/Phh1-dependent stress-sensing pathway. In Saccharomyces cerevisiae, Mpk1 is involved in cell wall integrity and functions downstream of the protein kinase C homolog. In contrast, in S. pombe, Pmk1 may not act in a linear manner with respect to fission yeast protein kinase C homologs. Interestingly, however, these two pathways are not independent; instead, they regulate cell integrity in a coordinate manner.

APA, Harvard, Vancouver, ISO, and other styles

29

Hylton, Hannah M., Bailey E. Lucas, and Ruben C. Petreaca. "Schizosaccharomyces pombe Assays to Study Mitotic Recombination Outcomes." Genes 11, no. 1 (January 10, 2020): 79. http://dx.doi.org/10.3390/genes11010079.

Full text

Abstract:

The fission yeast—Schizosaccharomyces pombe—has emerged as a powerful tractable system for studying DNA damage repair. Over the last few decades, several powerful in vivo genetic assays have been developed to study outcomes of mitotic recombination, the major repair mechanism of DNA double strand breaks and stalled or collapsed DNA replication forks. These assays have significantly increased our understanding of the molecular mechanisms underlying the DNA damage response pathways. Here, we review the assays that have been developed in fission yeast to study mitotic recombination.

APA, Harvard, Vancouver, ISO, and other styles

30

Roncero, Cesar, Rubén Celador, Noelia Sánchez, Patricia García, and Yolanda Sánchez. "The Role of the Cell Integrity Pathway in Septum Assembly in Yeast." Journal of Fungi 7, no. 9 (September 6, 2021): 729. http://dx.doi.org/10.3390/jof7090729.

Full text

Abstract:

Cytokinesis divides a mother cell into two daughter cells at the end of each cell cycle and proceeds via the assembly and constriction of a contractile actomyosin ring (CAR). Ring constriction promotes division furrow ingression, after sister chromatids are segregated to opposing sides of the cleavage plane. Cytokinesis contributes to genome integrity because the cells that fail to complete cytokinesis often reduplicate their chromosomes. While in animal cells, the last steps of cytokinesis involve extracellular matrix remodelling and mid-body abscission, in yeast, CAR constriction is coupled to the synthesis of a polysaccharide septum. To preserve cell integrity during cytokinesis, fungal cells remodel their cell wall through signalling pathways that connect receptors to downstream effectors, initiating a cascade of biological signals. One of the best-studied signalling pathways is the cell wall integrity pathway (CWI) of the budding yeast Saccharomyces cerevisiae and its counterpart in the fission yeast Schizosaccharomyces pombe, the cell integrity pathway (CIP). Both are signal transduction pathways relying upon a cascade of MAP kinases. However, despite strong similarities in the assembly of the septa in both yeasts, there are significant mechanistic differences, including the relationship of this process with the cell integrity signalling pathways.

APA, Harvard, Vancouver, ISO, and other styles

31

Papadopoulos, Ilias, David Gutiérrez-Moreno, Yifan Bo, Rubén Casillas, Phillip M. Greißel, Timothy Clark, Fernando Fernández-Lázaro, and Dirk M. Guldi. "Altering singlet fission pathways in perylene-dimers; perylene-diimide versus perylene-monoimide." Nanoscale 14, no. 13 (2022): 5194–203. http://dx.doi.org/10.1039/d1nr08523a.

Full text

Abstract:

The inherent differences on coplanarity and dipole moment in perylene-monoimides versus perylene-diimides and their impact on the singlet fission process were investigated in a series of phenylene- and naphthalene-linked dimers.

APA, Harvard, Vancouver, ISO, and other styles

32

Ni, Wenjun, Tianjiao Li, Christian Kloc, Licheng Sun, and Gagik G. Gurzadyan. "Singlet Fission, Polaron Generation and Intersystem Crossing in Hexaphenyl Film." Molecules 27, no. 16 (August 9, 2022): 5067. http://dx.doi.org/10.3390/molecules27165067.

Full text

Abstract:

The ultrafast dynamics of triplet excitons and polarons in hexaphenyl film was investigated by time-resolved fluorescence and femtosecond transient absorption techniques under various excitation photon energies. Two distinct pathways of triplet formation were clearly observed. Long-lived triplet states are populated within 4.5 ps via singlet fission-intersystem crossing, while the short-lived triplet states (1.5 ns) are generated via singlet fission from vibrational electronic states. In the meantime, polarons were formed from hot excitons on a timescale of <30 fs and recombined in ultrafast lifetime (0.37 ps). In addition, the characterization of hexaphenyl film suggests the morphologies of crystal and aggregate to wide applications in organic electronic devices. The present study provides a universally applicable film fabrication in hexaphenyl system towards future singlet fission-based solar cells.

APA, Harvard, Vancouver, ISO, and other styles

33

Jin, Quan-Wen, Samriddha Ray, Sung Hugh Choi, and Dannel McCollum. "The Nucleolar Net1/Cfi1-related Protein Dnt1 Antagonizes the Septation Initiation Network in Fission Yeast." Molecular Biology of the Cell 18, no. 8 (August 2007): 2924–34. http://dx.doi.org/10.1091/mbc.e06-09-0853.

Full text

Abstract:

The septation initiation network (SIN) and mitotic exit network (MEN) signaling pathways regulate cytokinesis and mitotic exit in the yeasts Schizosaccharomyces pombe, and Saccharomyces cerevisiae, respectively. One function of these pathways is to keep the Cdc14-family phosphatase, called Clp1 in S. pombe, from being sequestered and inhibited in the nucleolus. In S. pombe, the SIN and Clp1 act as part of a cytokinesis checkpoint that allows cells to cope with cytokinesis defects. The SIN promotes checkpoint function by 1) keeping Clp1 out of the nucleolus, 2) maintaining the cytokinetic apparatus, and 3) halting the cell cycle until cytokinesis is completed. In a screen for suppressors of the SIN mutant cytokinesis checkpoint defect, we identified a novel nucleolar protein called Dnt1 and other nucleolar proteins, including Rrn5 and Nuc1, which are known to be required for rDNA transcription. Dnt1 shows sequence homology to Net1/Cfi1, which encodes the nucleolar inhibitor of Cdc14 in budding yeast. Like Net1/Cfi1, Dnt1 is required for rDNA silencing and minichromosome maintenance, and both Dnt1 and Net1/Cfi1 negatively regulate the homologous SIN and MEN pathways. Unlike Net1/Cfi1, which regulates the MEN through the Cdc14 phosphatase, Dnt1 can inhibit SIN signaling independently of Clp1, suggesting a novel connection between the nucleolus and the SIN pathway.

APA, Harvard, Vancouver, ISO, and other styles

34

Wei, Wei, and Gary Ruvkun. "Lysosomal activity regulatesCaenorhabditis elegansmitochondrial dynamics through vitamin B12 metabolism." Proceedings of the National Academy of Sciences 117, no. 33 (July 31, 2020): 19970–81. http://dx.doi.org/10.1073/pnas.2008021117.

Full text

Abstract:

Mitochondrial fission and fusion are highly regulated by energy demand and physiological conditions to control the production, activity, and movement of these organelles. Mitochondria are arrayed in a periodic pattern inCaenorhabditis elegansmuscle, but this pattern is disrupted by mutations in the mitochondrial fission component dynamin DRP-1. Here we show that the dramatically disorganized mitochondria caused by a mitochondrial fission-defective dynamin mutation is strongly suppressed to a more periodic pattern by a second mutation in lysosomal biogenesis or acidification. Vitamin B12 is normally imported from the bacterial diet via lysosomal degradation of B12-binding proteins and transport of vitamin B12 to the mitochondrion and cytoplasm. We show that the lysosomal dysfunction induced by gene inactivations of lysosomal biogenesis or acidification factors causes vitamin B12 deficiency. Growth of theC. elegansdynamin mutant on anEscherichia colistrain with low vitamin B12 also strongly suppressed the mitochondrial fission defect. Of the twoC. elegansenzymes that require B12, gene inactivation of methionine synthase suppressed the mitochondrial fission defect of a dynamin mutation. We show that lysosomal dysfunction induced mitochondrial biogenesis, which is mediated by vitamin B12 deficiency and methionine restriction. S-adenosylmethionine, the methyl donor of many methylation reactions, including histones, is synthesized from methionine by S-adenosylmethionine synthase; inactivation of thesams-1S-adenosylmethionine synthase also suppresses thedrp-1fission defect, suggesting that vitamin B12 regulates mitochondrial biogenesis and then affects mitochondrial fission via chromatin pathways.

APA, Harvard, Vancouver, ISO, and other styles

35

Toda, Takashi, Itziar Ochotorena, and Kin-ichiro Kominami. "Two distinct ubiquitin-proteolysis pathways in the fission yeast cell cycle." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 354, no. 1389 (September 29, 1999): 1551–57. http://dx.doi.org/10.1098/rstb.1999.0498.

Full text

Abstract:

The SCF complex (Skp1-Cullin-1-F-box) and the APC/cyclosome (anaphase-promoting complex) are two ubiquitin ligases that play a crucial role in eukaryotic cell cycle control. In fission yeast F-box/WD-repeat proteins Pop1 and Pop2, components of SCF are required for cell-cycle-dependent degradation of the cyclin-dependent kinase (CDK) inhibitor Rum1 and the S-phase regulator Cdc18. Accumulation of these proteins in pop1 and pop2 mutants leads to re-replication and defects in sexual differentiation. Despite structural and functional similarities, Pop1 and Pop2 are not redundant homologues. Instead, these two proteins form heterodimers as well as homodimers, such that three distinct complexes, namely SCF Pop1/Pop1 , SCF Pop1/Pop2 and SCF Pop2/Pop2 , appear to exist in the cell. The APC/cyclosome is responsible for inactivation of CDK/cyclins through the degradation of B-type cyclins. We have identified two novel components or regulators of this complex, called Apc10 and Ste9, which are evolutionarily highly conserved. Apc10 (and Ste9), together with Rum1, are required for the establishment of and progression through the G1 phase in fission yeast. We propose that dual downregulation of CDK, one via the APC/cyclosome and the other via the CDK inhibitor, is a universal mechanism that is used to arrest the cell cycle at G1.

APA, Harvard, Vancouver, ISO, and other styles

36

Chapman, Elliott, Francesca Taglini, and Elizabeth H. Bayne. "Separable roles for RNAi in regulation of transposable elements and viability in the fission yeast Schizosaccharomyces japonicus." PLOS Genetics 18, no. 2 (February 28, 2022): e1010100. http://dx.doi.org/10.1371/journal.pgen.1010100.

Full text

Abstract:

RNA interference (RNAi) is a conserved mechanism of small RNA-mediated genome regulation commonly involved in suppression of transposable elements (TEs) through both post-transcriptional silencing, and transcriptional repression via heterochromatin assembly. The fission yeast Schizosaccharomyces pombe has been extensively utilised as a model for studying RNAi pathways. However, this species is somewhat atypical in that TEs are not major targets of RNAi, and instead small RNAs correspond primarily to non-coding pericentromeric repeat sequences, reflecting a specialised role for the pathway in promoting heterochromatin assembly in these regions. In contrast, in the related fission yeast Schizosaccharomyces japonicus, sequenced small RNAs correspond primarily to TEs. This suggests there may be fundamental differences in the operation of RNAi pathways in these two related species. To investigate these differences, we probed RNAi function in S. japonicus. Unexpectedly, and in contrast to S. pombe, we found that RNAi is essential in this species. Moreover, viability of RNAi mutants can be rescued by mutations implicated in enhancing RNAi-independent heterochromatin propagation. These rescued strains retain heterochromatic marks on TE sequences, but exhibit derepression of TEs at the post-transcriptional level. Our findings indicate that S. japonicus retains the ancestral role of RNAi in facilitating suppression of TEs via both post-transcriptional silencing and heterochromatin assembly, with specifically the heterochromatin pathway being essential for viability, likely due to a function in genome maintenance. The specialised role of RNAi in heterochromatin assembly in S. pombe appears to be a derived state that emerged after the divergence of S. japonicus.

APA, Harvard, Vancouver, ISO, and other styles

37

Collura, Ada, Joel Blaisonneau, Giuseppe Baldacci, and Stefania Francesconi. "The Fission Yeast Crb2/Chk1 Pathway Coordinates the DNA Damage and Spindle Checkpoint in Response to Replication Stress Induced by Topoisomerase I Inhibitor." Molecular and Cellular Biology 25, no. 17 (September 1, 2005): 7889–99. http://dx.doi.org/10.1128/mcb.25.17.7889-7899.2005.

Full text

Abstract:

ABSTRACT Living organisms experience constant threats that challenge their genome stability. The DNA damage checkpoint pathway coordinates cell cycle progression with DNA repair when DNA is damaged, thus ensuring faithful transmission of the genome. The spindle assembly checkpoint inhibits chromosome segregation until all chromosomes are properly attached to the spindle, ensuring accurate partition of the genetic material. Both the DNA damage and spindle checkpoint pathways participate in genome integrity. However, no clear connection between these two pathways has been described. Here, we analyze mutants in the BRCT domains of fission yeast Crb2, which mediates Chk1 activation, and provide evidence for a novel function of the Chk1 pathway. When the Crb2 mutants experience damaged replication forks upon inhibition of the religation activity of topoisomerase I, the Chk1 DNA damage pathway induces sustained activation of the spindle checkpoint, which in turn delays metaphase-to-anaphase transition in a Mad2-dependent fashion. This new pathway enhances cell survival and genome stability when cells undergo replicative stress in the absence of a proficient G2/M DNA damage checkpoint.

APA, Harvard, Vancouver, ISO, and other styles

38

Zhang, Guojie, and Marcus Müller. "Rupturing the hemi-fission intermediate in membrane fission under tension: Reaction coordinates, kinetic pathways, and free-energy barriers." Journal of Chemical Physics 147, no. 6 (August 14, 2017): 064906. http://dx.doi.org/10.1063/1.4997575.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Obolensky, O. I., I. A. Solov’yov, A. V. Solov’yov, and W. Greiner. "Fusion and fission of atomic clusters: recent advances." Computing Letters 1, no. 4 (March 6, 2005): 313–18. http://dx.doi.org/10.1163/157404005776611501.

Full text

Abstract:

We review recent advances made by our group in finding optimized geometries of atomic clusters as well as in description of fission of charged small metal clusters. We base our approach to these problems on analysis of multidimensional potential energy surface. For the fusion process we have developed an effective scheme of adding new atoms to stable cluster isomers which provides good starting points for a global optimization procedure and thus allows one to obtain optimal geometries of larger clusters in an efficient way. We apply this algorithm to finding geometries of metal and noble gas clusters. For the fission process the analysis of the potential energy landscape calculated on the ab initio level of theory allowed us to obtain very detailed information on energetics and pathways of the different fission channels for the Na2+ 10 clusters.

APA, Harvard, Vancouver, ISO, and other styles

40

Graham, Matt Werden. "(Invited) Controlling Interlayer Stacking Configuration to Optimize Exciton Extraction Pathways in Van Der Waals Materials." ECS Meeting Abstracts MA2022-01, no. 12 (July 7, 2022): 862. http://dx.doi.org/10.1149/ma2022-0112862mtgabs.

Full text

Abstract:

Employing ultrafast microscopy methods, we demonstrate how tuning the interlayer coupling by twisting stacking orientations results in different metastable electronic states like Moiré excitons in twisted bilayer graphene (tBLG) and bound triplet pairs (TT) in molecular crystals. Considering first tBLG, we show how stacking-angle tunable absorption resonances form a strongly-bound exciton state due to the interlayer orbitals' symmetric rehybridization. Using two-photon photoluminescence and intraband-transient absorption (TA) microscopies, we have imaged the photoemission and exciton dynamics from single-grains of tBLG. After resonant excitation, our results suggest the formation of strongly bound (up to 690 meV), metastable interlayer exciton states.[1] Our observation of resonant PL emission from twisted bilayer graphene materials is best explained by the theoretically predicted coexistence of strongly bound interlayer excitons and metallic graphene continuum states to form Moiré excitons. Unlike stacked graphene, semiconducting 2D transition metal dichalcogenides (TMDCs) have diffuse interlayer d-orbital overlap. To enhance interlayer electronic coupling in TMDCs, we apply an interlayer-directed E-field, inducing electron-hole dissociation as shown in Fig. 1b. Time-resolved photocurrents show that stacked WSe2 devices shown in Fig. 1a can have both IQE >50% and fast (<60 ps) picosecond electron escape times. Our ultrafast photocurrent rates kinetics give the same E-field-dependent electronic escape and dissociation rates seen from ultrafast optical TA microscopy.[2] To rationalize these fast electronic escape rates, we show the ratio of the electronic rates accurately predicts the actual WSe2 device photocurrent generation efficiency. Lastly, we will show how certain intermolecular twist angle packings of athraditiophene molecular crystals make electron-multiplication by singlet fission of TT states favorable. Singlet fission dynamics are indicated in Fig. 1c by the matching singlet (blue) vs. rising triplet dynamics (red) obtained when the probe polarization aligned along the crystal charge-transfer axis. However, other intermolecular packing angles (at 90o) instead localize and trap excitons as excimers, preventing singlet fission.[3] These interlayer stacked systems collectively demonstrate how remarkably different interlayer electronic states evolve from relatively small changes in interlayer twist angles in van der Waals stacked materials and molecular singlet fission materials. References [1] H. Patel, L. Huang, C.J. Kim, J. Park, M. W. Graham, Stacking Angle-Tunable Photoluminescence from Interlayer Exciton States in Twisted Bilayer Graphene, Nature Comm, 10, 1445 (2019) [2] K. T. Vogt, S.-F. Shi, F. Wang, M. W. Graham, Ultrafast photocurrent and absorption microscopy of few-layer TMD devices isolate rate-limiting dynamics driving fast and efficient photoresponse, J Phys Chem C, 124, 28, 15195–15204 (2020) [3] G. Mayonado, K. T. Vogt, J. Van Schenck, O. Ostroverkhova, M. W. Graham, Packing Morphology-Dependent Singlet Fission in Single Crystal Anthradithiophene Derivatives, OSA Technical Digest: Ultrafast Phenomena, doi.org/10.1364/UP.2020.Th2A.4 (2020) Figure 1

APA, Harvard, Vancouver, ISO, and other styles

41

Sharma, Priyanka, Lauren B. Ostermann, Sujan Piya, Baozhen Ke, Natalia Baran, Anudishi Tyagi, Muharrem Muftuoglu, et al. "ERK1/2 Inhibition Overcomes Resistance to Venetoclax in AML By Inhibiting Drp1 Dependent Mitochondrial Fission." Blood 142, Supplement 1 (November 28, 2023): 412. http://dx.doi.org/10.1182/blood-2023-185700.

Full text

Abstract:

Background: Primary or secondary resistance to venetoclax is frequently associated with mutational/non-mutational activation of MAPK pathways. ERK1/2 are terminal kinases in MAPK pathway and may be an appropriate target regardless of the upstream mechanisms that activate the pathway. ERK1/2 mediated phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth in RAS driven solid cancers (Kashatus et al., Mol Cell. 2015). However, the role of Drp1 dependent mitochondrial dynamics in therapeutic resistance in AML is unexplored. Methods: ERK1/2 was inhibited using Compound 27 (ERKi, Heightman et al., J Med Chem. 2018), an analog of ASTX029 (Munck et al., Mol Cancer Ther. 2021) in vitro and using ASTX029 in vivo. Preclinical models of venetoclax resistance and primary patient samples (n=8) were used to assess the synergy of concomitant Bcl2 and ERK1/2 inhibition (ERKi). In addition, a comprehensive analysis of alteration of signaling pathways, apoptotic signatures and DNA damage responses in response to ERKi+/-venetoclax were analyzed by mass cytometry based proteomic analysis (CyTOF) and immunoblotting. The potential clinical relevance of ERK1/2 inhibition to overcome venetoclax resistance was confirmed in a PDX model of AML (established from an AML patient who relapsed after venetoclax/decitabine treatment). Mitochondrial images were acquired using super-resolution imaging with OMX-Blaze followed by quantification with Imaris. Results : We previously reported the synergy of ERK1/2 inhibition using Compound 27 with venetoclax at inducing apoptosis in RAS mutated and/or venetoclax resistant AML cells including venetoclax resistant isogenic lines (Sharma et al., Blood 140; Supplement 1, 2022). Venetoclax+ERKi depleted leukemia progenitor cells in primary AML samples (CI:0.03-0.23) and impaired clonogenic growth of NRAS mutant PDX cells. In a PDX mouse model of post venetoclax/decitabine-relapsed AML, ASTX029+venetoclax treatment improved survival compared to vehicle (median survival 76.5 days vs. 50 days, p=0.0006) and venetoclax alone (median survival 76.5 days vs. 51.5 days, p=0.0065) (Figure 1) with corresponding reduction in leukemia burden in bone marrow (p<0.0001) and spleen (p<0.0001). CyTOF analysis using PDX bone marrow showed decreased expression of Mcl-1 and pMcl-1-T163 and an increased expression of BIM in response to ERKi+/-venetoclax (Figure 1). To maintain stemness in AML, mitochondrial ROS mitigation and Drp1-mediated mitochondrial fission are crucial (Schimmer et al., Cell Stem Cell. 2018). The inhibition of ERK1/2 resulted in decreased pDrp1-Ser616, along with an increase in mitochondrial length (p<0.001) suggesting impaired mitochondrial fission. This was accompanied by a decrease in mitochondrial membrane potential (p<0.0001) and an increase in mitochondrial ROS (p<0.0001). Overexpression (OE) of a phospho-mimetic i.e. Drp1-Ser616Glu-Ser637Ala led to shorter mitochondrial length (Figure 2), suggesting enhanced fission, a distinct metabolic phenotype with decreased ROS production and decreased mitochondrial depolarization with venetoclax+/- ERKi. Finally, Drp1 phospho-mimetic OE reversed apoptosis induction by venetoclax +/- ERKi (Figure 2) as compared to the wild-type and phospho-null (Ser616Ala) Drp1 (p<0.001) expressing cells, supporting the role of mitochondrial fission in resistance to venetoclax. Conclusion: The increased mitochondrial fission driven by ERK1/2 mediated phosphorylation of Drp1 contributes to venetoclax resistance in AML and inhibiting ERK1/2/Drp1 axis overcomes resistance to venetoclax by inhibiting mitochondrial fission (Figure 2). These data provide a strong rationale for the combination of ERK1/2 and Bcl-2 inhibitors in the treatment of AML.

APA, Harvard, Vancouver, ISO, and other styles

42

Romanello, Vanina, Marco Scalabrin, Mattia Albiero, Bert Blaauw, Luca Scorrano, and Marco Sandri. "Inhibition of the Fission Machinery Mitigates OPA1 Impairment in Adult Skeletal Muscles." Cells 8, no. 6 (June 15, 2019): 597. http://dx.doi.org/10.3390/cells8060597.

Full text

Abstract:

The maintenance of muscle mass and its ability to function relies on a bioenergetic efficient mitochondrial network. This network is highly impacted by fusion and fission events. We have recently shown that the acute deletion of the fusion protein Opa1 induces muscle atrophy, systemic inflammatory response, precocious epithelial senescence, and premature death that are caused by muscle-dependent secretion of FGF21. However, both fusion and fission machinery are suppressed in aging sarcopenia, cancer cachexia, and chemotherapy-induced muscle wasting. We generated inducible muscle-specific Opa1 and Drp1 double-knockout mice to address the physiological relevance of the concomitant impairment of fusion and fission machinery in skeletal muscle. Here we show that acute ablation of Opa1 and Drp1 in adult muscle causes the accumulation of abnormal and dysfunctional mitochondria, as well as the inhibition of autophagy and mitophagy pathways. This ultimately results in ER stress, muscle loss, and the reduction of force generation. However, the simultaneous inhibition of the fission protein Drp1 when Opa1 is absent alleviates FGF21 induction, oxidative stress, denervation, and inflammation rescuing the lethal phenotype of Opa1 knockout mice, despite the presence of any muscle weakness. Thus, the simultaneous inhibition of fusion and fission processes mitigates the detrimental effects of unbalanced mitochondrial fusion and prevents the secretion of pro-senescence factors.

APA, Harvard, Vancouver, ISO, and other styles

43

Osman, Christof, Thomas R. Noriega, Voytek Okreglak, Jennifer C. Fung, and Peter Walter. "Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion." Proceedings of the National Academy of Sciences 112, no. 9 (February 17, 2015): E947—E956. http://dx.doi.org/10.1073/pnas.1501737112.

Full text

Abstract:

Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. We developed a LacO-LacI system to noninvasively image mtDNA dynamics in living cells. Using this system, we found that nucleoids are nonrandomly spaced within the mitochondrial network and observed the spatiotemporal events involved in mtDNA inheritance. Surprisingly, cells deficient in mitochondrial fusion and fission distributed and inherited mtDNA normally, pointing to alternative pathways involved in these processes. We identified such a mechanism, where we observed fission-independent, but F-actin–dependent, tip generation that was linked to the positioning of mtDNA to the newly generated tip. Although mitochondrial fusion and fission were dispensable for mtDNA distribution and inheritance, we show through a combination of genetics and next-generation sequencing that their absence leads to an accumulation of mitochondrial genomes harboring deleterious structural variations that cluster at the origins of mtDNA replication, thus revealing crucial roles for mitochondrial fusion and fission in maintaining the integrity of the mitochondrial genome.

APA, Harvard, Vancouver, ISO, and other styles

44

Amato, F., M. Bansal, C. Cosentino, W. Curatola, and D. di Bernardo. "IDENTIFICATION OF REGULATORY PATHWAYS OF THE CELL CYCLE IN FISSION YEAST." IFAC Proceedings Volumes 39, no. 18 (2006): 153–58. http://dx.doi.org/10.3182/20060920-3-fr-2912.00031.

Full text

APA, Harvard, Vancouver, ISO, and other styles

45

Huang, Xinhe, Markos Leggas, and Robert C. Dickson. "Correction: Drug Synergy Drives Conserved Pathways to Increase Fission Yeast Lifespan." PLOS ONE 10, no. 4 (April 29, 2015): e0125857. http://dx.doi.org/10.1371/journal.pone.0125857.

Full text

APA, Harvard, Vancouver, ISO, and other styles

46

Pool, René, and Peter G. Bolhuis. "Sampling the kinetic pathways of a micelle fusion and fission transition." Journal of Chemical Physics 126, no. 24 (June 28, 2007): 244703. http://dx.doi.org/10.1063/1.2741513.

Full text

APA, Harvard, Vancouver, ISO, and other styles

47

Chen, Dongrong, Caroline R. M. Wilkinson, Stephen Watt, Christopher J. Penkett, W. Mark Toone, Nic Jones, and Jürg Bähler. "Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast." Molecular Biology of the Cell 19, no. 1 (January 2008): 308–17. http://dx.doi.org/10.1091/mbc.e07-08-0735.

Full text

Abstract:

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.

APA, Harvard, Vancouver, ISO, and other styles

48

Low, C. P., G. Shui, L. P. Liew, S. Buttner, F. Madeo, I. W. Dawes, M. R. Wenk, and H. Yang. "Caspase-dependent and -independent lipotoxic cell-death pathways in fission yeast." Journal of Cell Science 121, no. 16 (July 24, 2008): 2671–84. http://dx.doi.org/10.1242/jcs.028977.

Full text

APA, Harvard, Vancouver, ISO, and other styles

49

Nyinawabera, Angelique, Smiti Gupta, Karthikeyan Chandrabose, and Amit K. Tiwari. "Targeting dysregulated mitochondrial fission pathways in triple negative breast cancer therapy." Proceedings for Annual Meeting of The Japanese Pharmacological Society WCP2018 (2018): PO2–10–26. http://dx.doi.org/10.1254/jpssuppl.wcp2018.0_po2-10-26.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Bamford, Karlee L., Saurabh S. Chitnis, Rhonda L. Stoddard, J. Scott McIndoe, and Neil Burford. "Bond fission in monocationic frameworks: diverse fragmentation pathways for phosphinophosphonium cations." Chemical Science 7, no. 4 (2016): 2544–52. http://dx.doi.org/10.1039/c5sc03804a.

Full text

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Fission pathways'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles