Parkin and PINK1 Function in a Vesicular Trafficking Pathway Regulating Mitochondrial Quality Control

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2014 Jan 22

PMID 24446486

Citations 389

Authors

Gian-Luca McLelland

Vincent Soubannier

Carol X Chen

Heidi M McBride

Edward A Fon

Affiliations

Soon will be listed here.

Abstract

Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). Parkin and PINK1, two genes associated with familial PD, have been implicated in the degradation of depolarized mitochondria via autophagy (mitophagy). Here, we describe the involvement of parkin and PINK1 in a vesicular pathway regulating mitochondrial quality control. This pathway is distinct from canonical mitophagy and is triggered by the generation of oxidative stress from within mitochondria. Wild-type but not PD-linked mutant parkin supports the biogenesis of a population of mitochondria-derived vesicles (MDVs), which bud off mitochondria and contain a specific repertoire of cargo proteins. These MDVs require PINK1 expression and ultimately target to lysosomes for degradation. We hypothesize that loss of this parkin- and PINK1-dependent trafficking mechanism impairs the ability of mitochondria to selectively degrade oxidized and damaged proteins leading, over time, to the mitochondrial dysfunction noted in PD.

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