Pryde, KR;
Smith, HL;
Chau, KY;
Schapira, AH;
(2016)
PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy.
Journal of Cell Biology
, 213
(2)
pp. 163-171.
10.1083/jcb.201509003.
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Pryde et al 2016 PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy VOR.pdf Download (2MB) | Preview |
Abstract
Mitochondrial fission is essential for the degradation of damaged mitochondria. It is currently unknown how the dynamin-related protein 1 (DRP1)-associated fission machinery is selectively targeted to segregate damaged mitochondria. We show that PTEN-induced putative kinase (PINK1) serves as a pro-fission signal, independently of Parkin. Normally, the scaffold protein AKAP1 recruits protein kinase A (PKA) to the outer mitochondrial membrane to phospho-inhibit DRP1. We reveal that after damage, PINK1 triggers PKA displacement from A-kinase anchoring protein 1. By ejecting PKA, PINK1 ensures the requisite fission of damaged mitochondria for organelle degradation. We propose that PINK1 functions as a master mitophagy regulator by activating Parkin and DRP1 in response to damage. We confirm that PINK1 mutations causing Parkinson disease interfere with the orchestration of selective fission and mitophagy by PINK1.
| Type: | Article |
|---|---|
| Title: | PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1083/jcb.201509003 |
| Publisher version: | http://dx.doi.org/10.1083/jcb.201509003 |
| Language: | English |
| Additional information: | Copyright © 2016 Pryde et al. Published by The Rockefeller University Press and available at http://dx.doi.org/10.1083/jcb.201509003. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/) |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1482629 |
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