dc.contributor.author | MARTIN, SEAMUS | en |
dc.date.accessioned | 2015-12-14T12:56:06Z | |
dc.date.available | 2015-12-14T12:56:06Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.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, 451-466 | en |
dc.identifier.issn | 10972765 | en |
dc.identifier.other | Y | en |
dc.description | PUBLISHED | en |
dc.description.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. | en |
dc.format.extent | 451-466 | en |
dc.relation.ispartofseries | Molecular Cell | en |
dc.relation.ispartofseries | 55 | en |
dc.relation.ispartofseries | 3 | en |
dc.rights | Y | en |
dc.subject | Toll-like receptors | en |
dc.title | Bcl-2 family proteins participate in mitochondrial quality control by regulating parkin/PINK1-dependent mitophagy | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/martinsj | en |
dc.identifier.rssinternalid | 98545 | en |
dc.identifier.doi | http://dx.doi.org/10.1016/j.molcel.2014.06.001 | en |
dc.rights.ecaccessrights | openAccess | |
dc.identifier.uri | http://hdl.handle.net/2262/75313 | |