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Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway

Shen, James L
Fortier, Tina M
Wang, Ruoxi
Baehrecke, Eric H
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Abstract

Defects in autophagy cause problems in metabolism, development, and disease. The autophagic clearance of mitochondria, mitophagy, is impaired by the loss of Vps13D. Here, we discover that Vps13D regulates mitophagy in a pathway that depends on the core autophagy machinery by regulating Atg8a and ubiquitin localization. This process is Pink1 dependent, with loss of pink1 having similar autophagy and mitochondrial defects as loss of vps13d. The role of Pink1 has largely been studied in tandem with Park/Parkin, an E3 ubiquitin ligase that is widely considered to be crucial in Pink1-dependent mitophagy. Surprisingly, we find that loss of park does not exhibit the same autophagy and mitochondrial deficiencies as vps13d and pink1 mutant cells and contributes to mitochondrial clearance through a pathway that is parallel to vps13d. These findings provide a Park-independent pathway for Pink1-regulated mitophagy and help to explain how Vps13D regulates autophagy and mitochondrial morphology and contributes to neurodegenerative diseases.

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Shen JL, Fortier TM, Wang R, Baehrecke EH. Vps13D functions in a Pink1-dependent and Parkin-independent mitophagy pathway. J Cell Biol. 2021 Nov 1;220(11):e202104073. doi: 10.1083/jcb.202104073. Epub 2021 Aug 30. PMID: 34459871; PMCID: PMC8406608.

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10.1083/jcb.202104073
PubMed ID
34459871
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© 2021 Shen et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).; Attribution-NonCommercial-ShareAlike 4.0 International