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dc.contributor.authorTar, Krisztina
dc.contributor.authorDange, Thomas
dc.contributor.authorYang, Ciyu
dc.contributor.authorYao, Yanhua
dc.contributor.authorBulteau, Anne-Laure
dc.contributor.authorSalcedo, Elena Fernandez
dc.contributor.authorBraigen, Stephen
dc.contributor.authorBouillaud, Frederic
dc.contributor.authorFinley, Daniel
dc.contributor.authorSchmidt, Marion
dc.date.accessioned2019-10-05T09:46:36Z
dc.date.issued2014
dc.identifier.citationTar, Krisztina, Thomas Dange, Ciyu Yang, Yanhua Yao, Anne-Laure Bulteau, Elena Fernandez Salcedo, Stephen Braigen, Frederic Bouillaud, Daniel Finley, and Marion Schmidt. 2014. “Proteasomes Associated with the Blm10 Activator Protein Antagonize Mitochondrial Fission through Degradation of the Fission Protein Dnm1.” Journal of Biological Chemistry 289 (17): 12145–56. https://doi.org/10.1074/jbc.m114.554105.
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483148*
dc.description.abstractBackground: Blm10 binds to the proteasome core particle and stimulates its proteolytic activity. Results: Loss of BLM10 results in impaired respiration, elevated oxidative stress sensitivity, increased mitochondrial fission, and stabilization of the fission protein Dnm1. Conclusion: Blm10 proteasome-mediated Dnm1 degradation is a regulatory mechanism to maintain correct mitochondrial function. Significance: Blm10 is involved in mitochondrial quality control under oxidative stress.The conserved Blm10/PA200 activators bind to the proteasome core particle gate and facilitate turnover of peptides and unfolded proteins in vitro. We report here that Blm10 is required for the maintenance of functional mitochondria. BLM10 expression is induced 25-fold upon a switch from fermentation to oxidative metabolism. In the absence of BLM10, Saccharomyces cerevisiae cells exhibit a temperature-sensitive growth defect under oxidative growth conditions and produce colonies with dysfunctional mitochondria at high frequency. Loss of BLM10 leads to reduced respiratory capacity, increased mitochondrial oxidative damage, and reduced viability in the presence of oxidative stress or death stimuli. In the absence of BLM10, increased fragmentation of the mitochondrial network under oxidative stress is observed indicative of elevated activity of the mitochondrial fission machinery. The degradation of Dnm1, the main factor mediating mitochondrial fission, is impaired in the absence of BLM10 in vitro and in vivo. These data suggest that the mitochondrial functional and morphological changes observed are related to elevated Dnm1 levels. This hypothesis is supported by the finding that cells that constitutively overexpress DNM1 display the same mitochondrial defects as blm10 cells. The data are consistent with a model in which Blm10 proteasome-mediated turnover of Dnm1 is required for the maintenance of mitochondrial function and provides cytoprotection under conditions that induce increased mitochondrial damage and programmed cell death.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dash.licenseLAA
dc.titleProteasomes Associated with the Blm10 Activator Protein Antagonize Mitochondrial Fission through Degradation of the Fission Protein Dnm1
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Biological Chemistry
dash.depositing.authorFinley, Daniel::55733c495443e58aeebdb3090cda00e5::600
dc.date.available2019-10-05T09:46:36Z
dash.workflow.comments1Science Serial ID 109898
dc.identifier.doi10.1074/jbc.M114.554105
dash.source.volume289;17
dash.source.page12145


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