Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. (20th January 2014)

• Record Type: Journal Article
• Authors: McLelland, Gian‐Luca; Soubannier, Vincent; Chen, Carol X; McBride, Heidi M; Fon, Edward A
• Is Part Of: EMBO journal. Volume 33:Number 4(2014)
• Page Start: 282
• Page End: 295
• Publication Date: 2014-01-20
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1002/embj.201385902
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="main" id="embj201385902-abs-0001"> <title>Abstract</title> <p>Mitochondrial dysfunction has long been associated with Parkinson's disease (PD). <italic>Parkin</italic> and <italic>PINK1</italic>, 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.</p> </abstract>