Toggle Main Menu Toggle Search

Open Access padlockePrints

NDP52 acts as a redox sensor in PINK1/Parkin-mediated mitophagy

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 Yue, Dr Agnieszka Bronowska, Dr Viktor Korolchuk

Downloads


Licence

This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 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.


Publication metadata

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


Altmetrics

Altmetrics provided by Altmetric


Funding

Funder referenceFunder name
101062916
2018/D/LD/MC/8
218547/Z/19/Z
BB/R008167/2
BB/M023389/1Biotechnology and Biological Sciences Research Council (BBSRC)
DP200100347
FWF SFB F79
FT1601100063
GNT1106471
GNT1160315
IEC\NSFC\170125Royal Society

Share