Parkin Sensitizes toward Apoptosis Induced by Mitochondrial Depolarization through Promoting Degradation of Mcl-1
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, 1538-1553Download Item:
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.
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http://people.tcd.ie/martinsjDescription:
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Author: MARTIN, SEAMUS
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Journal ArticleCollections
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Cell Reports9
4
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http://dx.doi.org/10.1016/j.celrep.2014.10.046Metadata
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