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Lookup NU author(s): Dr Tetsushi Kataura, Gisela Otten, Dr Yoana Rabanal Ruiz, Francesca Urselli, Dr Filippo Scialo, Lanyu Fan, Dr Graham Smith, Professor Wyatt YueORCiD, Dr Agnieszka Bronowska, Professor Viktor KorolchukORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2022 The Authors. Published under the terms of the CC BY 4.0 license.Mitophagy, the elimination of mitochondria via the autophagy-lysosome pathway, is essential for the maintenance of cellular homeostasis. The best characterised mitophagy pathway is mediated by stabilisation of the protein kinase PINK1 and recruitment of the ubiquitin ligase Parkin to damaged mitochondria. Ubiquitinated mitochondrial surface proteins are recognised by autophagy receptors including NDP52 which initiate the formation of an autophagic vesicle around the mitochondria. Damaged mitochondria also generate reactive oxygen species (ROS) which have been proposed to act as a signal for mitophagy, however the mechanism of ROS sensing is unknown. Here we found that oxidation of NDP52 is essential for the efficient PINK1/Parkin-dependent mitophagy. We identified redox-sensitive cysteine residues involved in disulphide bond formation and oligomerisation of NDP52 on damaged mitochondria. Oligomerisation of NDP52 facilitates the recruitment of autophagy machinery for rapid mitochondrial degradation. We propose that redox sensing by NDP52 allows mitophagy to function as a mechanism of oxidative stress response.
Author(s): Kataura T, Otten EG, Rabanal-Ruiz Y, Adriaenssens E, Urselli F, Scialo F, Fan L, Smith GR, Dawson WM, Chen X, Yue WW, Bronowska AK, Carroll B, Martens S, Lazarou M, Korolchuk VI
Publication type: Article
Publication status: Published
Journal: EMBO Journal
Year: 2022
Volume: 42
Pages: 1-16
Online publication date: 14/12/2022
Acceptance date: 11/11/2022
Date deposited: 04/01/2023
ISSN (print): 0261-4189
ISSN (electronic): 1460-2075
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.15252/embj.2022111372
DOI: 10.15252/embj.2022111372
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