TY  - JOUR
AU  - Lechado-Terradas, Anna
AU  - Schepers, Sandra
AU  - Zittlau, Katharina I.
AU  - Sharma, Karan
AU  - Ok, Orkun
AU  - Fitzgerald, Julia C.
AU  - Geimer, Stefan
AU  - Westermann, Benedikt
AU  - Macek, Boris
AU  - Kahle, Philipp
TI  - Parkin-dependent mitophagy occurs via proteasome-dependent steps sequentially targeting separate mitochondrial sub-compartments for autophagy
JO  - Autophagy reports
VL  - 1
IS  - 1
SN  - 2769-4127
CY  - London
PB  - Taylor & Francis Group
M1  - DZNE-2023-01158
SP  - 576 - 602
PY  - 2022
AB  - 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.
LB  - PUB:(DE-HGF)16
DO  - DOI:10.1080/27694127.2022.2143214
UR  - https://pub.dzne.de/record/266473
ER  -