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

Autor:	Pryde KR; Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, England, UK k.pryde@ucl.ac.uk., Smith HL; Faculty of Brain Sciences, University College London, London W1T 7NF, England, UK., Chau KY; Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, England, UK., Schapira AH; Department of Clinical Neurosciences, Institute of Neurology, University College London, London NW3 2PF, England, UK.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2016 Apr 25; Vol. 213 (2), pp. 163-71. Date of Electronic Publication: 2016 Apr 18.
DOI:	10.1083/jcb.201509003
Abstrakt:	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. (© 2016 Pryde et al.)
Databáze:	MEDLINE
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