Mitophagy restricts BAX/BAK-independent, Parkin-mediated apoptosis
Using in vitro and in vivo models and two different whole genome screening approaches, we report that Parkin expression sensitized cells to die, that this process required the kinase activity of PINK1 and the degradation activity of the UPS. This process of cell death was independent of the B-cell lymphoma 2 (Bcl2) family members but involved caspase activation mediated by assembly of the apoptosome. We found that Parkin-dependent cytochrome c (cyt c) release from the inter-membrane space was mediated by UPS activity on the OMM and that lysosomal degradation of mitochondrial remnants protected from cell death. Finally, we identified the recognition of ubiquitinated OMM proteins by autophagy receptors as a cell fate decision point downstream the activation of the PINK1-Parkin axis.