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dc.contributor.authorOshima, Yumiko
dc.contributor.authorCartier, Etienne
dc.contributor.authorBoyman, Liron
dc.contributor.authorVerhoeven, Nicolas
dc.contributor.authorPolster, Brian M
dc.contributor.authorHuang, Weiliang
dc.contributor.authorKane, Maureen
dc.contributor.authorLederer, W Jonathan
dc.contributor.authorKarbowski, Mariusz
dc.date.accessioned2021-04-26T19:31:47Z
dc.date.available2021-04-26T19:31:47Z
dc.date.issued2021-04-14en_US
dc.identifier.urihttp://hdl.handle.net/10713/15504
dc.description.abstractHere, we report that acute reduction in mitochondrial translation fidelity (MTF) causes ubiquitination of the inner mitochondrial membrane (IMM) proteins, including TRAP1 and CPOX, which occurs selectively in mitochondria with a severed outer mitochondrial membrane (OMM). Ubiquitinated IMM recruits the autophagy machinery. Inhibiting autophagy leads to increased accumulation of mitochondria with severed OMM and ubiquitinated IMM. This process occurs downstream of the accumulation of cytochrome c/CPOX in a subset of mitochondria heterogeneously distributed throughout the cell ("mosaic distribution"). Formation of mosaic mitochondria, OMM severing, and IMM ubiquitination require active mitochondrial translation and mitochondrial fission, but not the proapoptotic proteins Bax and Bak. In contrast, in Parkin-overexpressing cells, MTF reduction does not lead to the severing of the OMM or IMM ubiquitination, but it does induce Drp1-independent ubiquitination of the OMM. Furthermore, high-cytochrome c/CPOX mitochondria are preferentially targeted by Parkin, indicating that in the context of reduced MTF, they are mitophagy intermediates regardless of Parkin expression. In sum, Parkin-deficient cells adapt to mitochondrial proteotoxicity through a Drp1-mediated mechanism that involves the severing of the OMM and autophagy targeting ubiquitinated IMM proteins. © 2021 Oshima et al.en_US
dc.description.urihttps://doi.org/10.1083/jcb.202006043en_US
dc.language.isoenen_US
dc.publisherRockefeller University Pressen_US
dc.relation.ispartofJournal of Cell Biologyen_US
dc.rights© 2021 Oshima et al.en_US
dc.subjectParkinen_US
dc.subject.meshMitochondrial Membranesen_US
dc.subject.meshMitophagyen_US
dc.subject.meshUbiquitinationen_US
dc.titleParkin-independent mitophagy via Drp1-mediated outer membrane severing and inner membrane ubiquitinationen_US
dc.typeArticleen_US
dc.identifier.doi10.1083/jcb.202006043
dc.identifier.pmid33851959
dc.source.volume220
dc.source.issue6
dc.source.countryUnited States


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