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Parkin and PINK 1 function in a vesicular trafficking pathway regulating mitochondrial quality control
Author(s) -
McLelland GianLuca,
Soubannier Vincent,
Chen Carol X,
McBride Heidi M,
Fon Edward A
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201385902
Subject(s) - biology , pink1 , parkin , microbiology and biotechnology , mitochondrion , function (biology) , genetics , mitophagy , autophagy , apoptosis , medicine , disease , pathology , parkinson's disease
Mitochondrial dysfunction has long been associated with P arkinson's disease ( PD ). Parkin and PINK 1 , 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 PINK 1 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 ( MDV s), which bud off mitochondria and contain a specific repertoire of cargo proteins. These MDV s require PINK 1 expression and ultimately target to lysosomes for degradation. We hypothesize that loss of this parkin‐ and PINK 1‐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 .