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PINK1 disables the anti-fission machinery to segregate damaged mitochondria for mitophagy

Authors :
Kai-Yin Chau
Heather L. Smith
Kenneth Robert Pryde
Anthony H.V. Schapira
Source :
The Journal of Cell Biology
Publication Year :
2016
Publisher :
Rockefeller University Press, 2016.

Abstract

In addition to recruiting Parkin/autophagy receptors to damaged mitochondria, the authors show that PINK1 triggers PKA displacement from AKAP1 after damage to trigger mitochondrial fission in a Parkin-independent manner, suggesting that PINK1 is a master mitophagy regulator.<br />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.

Details

ISSN :
15408140 and 00219525
Volume :
213
Database :
OpenAIRE
Journal :
Journal of Cell Biology
Accession number :
edsair.doi.dedup.....3f74be99874c09c276c69a274a3c9ad8