Bcl-2 family proteins participate in mitochondrial quality control by regulating parkin/PINK1-dependent mitophagy
Citation:
Hollville,Ã milie E., Carroll,Richard G. R.G., Cullen,Sean P. S.P., Martin,Seamus J. S.J., Bcl-2 family proteins participate in mitochondrial quality control by regulating parkin/PINK1-dependent mitophagy, Molecular Cell, 55, 3, 2014, 451-466Download Item:
Abstract:
Mitophagy facilitates the selective elimination of impaired or depolarized mitochondria through targeting the latter to autophagosomes. Parkin becomes localized to depolarized mitochondria in a PINK1-dependent manner and polyubiquitinates multiple mitochondrial outer membrane proteins. This permits ubiquitin-binding proteins (e.g., p62 and NBR1) to target impaired mitochondria to autophagosomes via Atg8/LC3II. Bcl-2 family proteins regulate mitochondrial outer membrane permeabilization during apoptosis and can also influence macroautophagy via interactions with Beclin-1. Here, we show that Parkin-dependent mitophagy is antagonized by prosurvival members of the Bcl-2 family (e.g., Bcl-xL and Mcl-1) in a Beclin-1-independent manner. Bcl-2 proteins suppressed mitophagy through inhibition of Parkin translocation to depolarized mitochondria. Consistent with this, Parkin translocation to mitochondria was enhanced by BH3-only proteins or a BH3-only mimetic. Taken together with their role as regulators of apoptosis-associated mitochondrial permeabilization, as well as mitochondrial fission/fusion dynamics, this suggests that Bcl-2 family proteins act as global regulators of mitochondrial homeostasis.
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http://people.tcd.ie/martinsjDescription:
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Author: MARTIN, SEAMUS
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Journal ArticleCollections
Series/Report no:
Molecular Cell55
3
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Full text availableKeywords:
Toll-like receptorsDOI:
http://dx.doi.org/10.1016/j.molcel.2014.06.001ISSN:
10972765Metadata
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