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- W2169368410 abstract "Mitochondrial dynamics play crucial roles in mitophagy-based mitochondrial quality control, but how these pathways are regulated to meet cellular energy demands remains obscure. Using non-transformed human RPE1 cells, we report that upregulation of mitochondrial OXPHOS alters mitochondrial dynamics to inhibit Parkin-mediated mitophagy. Despite basal mitophagy rates remaining stable upon switch to OXPHOS-dependency, mitochondria resist fragmentation when RPE1 cells are treated with the protonophore, CCCP. Mechanistically, this is because cleavage of the inner membrane fusion factor L-OPA1 is prevented due to the failure to activate the inner membrane protease OMA1 in mitochondria with collapsed membrane potential. In parallel, OXPHOS-active mitochondria are protected from damage-induced fission, through impaired recruitment and activation of mitochondrial DRP1. Using OMA1-deficient MEFs, we show that the preservation of a stable pool of L-OPA1 at the inner mitochondrial membrane is sufficient to delay mitophagy, even in the presence of Parkin. The capacity of OXPHOS-dependent cells to maintain significant mitochondrial content in the face of acute damage has important implications for mitochondrial quality control in vivo." @default.
- W2169368410 created "2016-06-24" @default.
- W2169368410 creator A5064962610 @default.
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- W2169368410 date "2014-01-01" @default.
- W2169368410 modified "2023-09-26" @default.
- W2169368410 title "Impaired OMA1 dependent OPA1 cleavage and reduced DRP1 fission activity combine to prevent mitophagy in OXPHOS dependent cells" @default.
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- W2169368410 doi "https://doi.org/10.1242/jcs.144337" @default.
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