Journal Article

DZNE-2023-01158

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Parkin-dependent mitophagy occurs via proteasome-dependent steps sequentially targeting separate mitochondrial sub-compartments for autophagy

Lechado-Terradas, A. ; Schepers, S. ; Zittlau, K. I. ; Sharma, K. ; Ok, O. ; Fitzgerald, J. C. ; Geimer, S. ; Westermann, B. ; Macek, B. ; Kahle, P. (Last author)DZNE*

2022
Taylor & Francis Group London

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Please use a persistent id in citations: doi:10.1080/27694127.2022.2143214

Abstract: PINK1/parkin-dependent mitophagy initially involves (phospho)ubiquitin-directed proteasome-dependent degradation of certain outer mitochondrial membrane (OMM) proteins (e.g. mitofusins) and the recruitment of autophagy adaptors to a group of ubiquitinated OMM proteins, eventually leading to autophagic removal of damaged mitochondria in stressed cells. Here we provide evidence that mitochondrial degradation occurs via stepwise delivery of separate mitochondrial sub-compartments for autophagic degradation. OMM and inner mitochondrial material appears to become separately isolated for autophagolysosomal degradation, not only in parkin-overexpressing HeLa cells but also in cells that express endogenous parkin (human embryonic kidney cells and neural progenitor cells) with slower mitophagy kinetics. The remaining inner mitochondrial material becomes degraded only after much prolonged membrane depolarization, potentially involving another proteasome-sensitive step. The present combined microscopy and proteomics analyses support the idea that cell stress-induced parkin-dependent mitophagy is a complex multi-step process with distinct mitochondrial sub-compartments being separately targeted for autophagic degradation.

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Contributing Institute(s):

1. Functional Neurogenetics (AG Kahle)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2022

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