Mitochondrial Fission, Integrity and Completion of Mitophagy Require Separable Functions of Vps13D in Drosophila Neurons

Insolera, Ryan and Lőrincz, Péter and Wishnie, Alec J. and Juhász, Gábor and Collins, Catherine A. (2021) Mitochondrial Fission, Integrity and Completion of Mitophagy Require Separable Functions of Vps13D in Drosophila Neurons. PLOS GENETICS, 17 (8). pp. 1-28. ISSN 1553-7390 (print); 1553-7404 (online)

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Abstract

A healthy population of mitochondria, maintained by proper fission, fusion, and degradation, is critical for the long-term survival and function of neurons. Here, our discovery of mitophagy intermediates in fission-impaired Drosophila neurons brings new perspective into the relationship between mitochondrial fission and mitophagy. Neurons lacking either the ataxia disease gene Vps13D or the dynamin related protein Drp1 contain enlarged mitochondria that are engaged with autophagy machinery and also lack matrix components. Reporter assays combined with genetic studies imply that mitophagy both initiates and is completed in Drp1 impaired neurons, but fails to complete in Vps13D impaired neurons, which accumulate compromised mitochondria within stalled mito-phagophores. Our findings imply that in fission-defective neurons, mitophagy becomes induced, and that the lipid channel containing protein Vps13D has separable functions in mitochondrial fission and phagophore elongation.

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