Journal
JOURNAL OF CELL BIOLOGY
Volume 213, Issue 2, Pages 163-171Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201509003
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Funding
- Wellcome Trust/Medical Research Council Joint Call in Neurodegeneration award [WT089698]
- Centre of Excellence in Neurodegeneration award [MR/J009660/1]
- National Institute of Health Research grants [RCF30AS2012, RCF73TS20145989, RCF103/AS/2014]
- Medical Research Council [MR/J009660/1] Funding Source: researchfish
- MRC [MR/J009660/1] Funding Source: UKRI
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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.
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