dc.contributor.author | MARTIN, SEAMUS | en |
dc.date.accessioned | 2015-01-06T15:15:51Z | |
dc.date.available | 2015-01-06T15:15:51Z | |
dc.date.issued | 2014 | en |
dc.date.submitted | 2014 | en |
dc.identifier.citation | Carroll,Richard G. R.G., Hollville,Ã milie E., Martin,Seamus S., Parkin Sensitizes toward Apoptosis Induced by Mitochondrial Depolarization through Promoting Degradation of Mcl-1, Cell Reports, 9, 4, 2014, 1538-1553 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/72930 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Mitochondrial depolarization promotes Parkin- and PTEN-induced kinase 1 (PINK1)-dependent polyubiquitination of multiple proteins on mitochondrial outer membranes, resulting in the removal of defective mitochondria via mitophagy. Because Parkin mutations occur in Parkinson’s disease, a condition associated with the death of dopaminergic neurons in the midbrain, wild-type Parkin is thought to promote neuronal survival. However, here we show that wild-type Parkin greatly sensitized toward apoptosis induced by mitochondrial depolarization but not by proapoptotic stimuli that failed to activate Parkin. Parkin-dependent apoptosis required PINK1 and was efficiently blocked by prosurvival members of the Bcl-2 family or knockdown of Bax and Bak. Upon mitochondrial depolarization, the Bcl-2 family member Mcl-1 underwent rapid Parkin- and PINK1-dependent polyubiquitination and degradation, which sensitized toward apoptosis via opening of the Bax/Bak channel. These data suggest that similar to other sensors of cell stress, such as p53, depending on the degree of mitochondrial damage. | en |
dc.description.sponsorship | We thank Dr. Stephen Tait for provision of GFP-Parkin-expressing HeLa cells, Dr. Richard Youle for provision of mCherry-Parkin and YFP-Parkin plasmids, Dr. Dennis J. Selkoe for provision of PINK1-FLAG plasmid, and Dr. Maria Soengas for provision of shRNA plasmids targeted against Bax and Bak. The S.J.M. laboratory is supported by PI (08/IN.1/B2031) and SRC (07/SRC/B1144) grants from Science Foundation Ireland. S.J.M. is a Science Foundation Ireland Principal Investigator | en |
dc.format.extent | 1538-1553 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Cell Reports | en |
dc.relation.ispartofseries | 9 | en |
dc.relation.ispartofseries | 4 | en |
dc.rights | Y | en |
dc.subject | Parkin has cytoprotective (mitophagy) or cytotoxic modes (apoptosis), | en |
dc.subject.lcsh | Parkin has cytoprotective (mitophagy) or cytotoxic modes (apoptosis), | en |
dc.title | Parkin Sensitizes toward Apoptosis Induced by Mitochondrial Depolarization through Promoting Degradation of Mcl-1 | 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 | 98541 | en |
dc.identifier.doi | http://dx.doi.org/10.1016/j.celrep.2014.10.046 | en |
dc.rights.ecaccessrights | openAccess | |