Fig. 7.

Alternative, autophagy-independent modes of mitochondrial processing by endolysosomes. a Under sub-threshold conditions of mitochondrial stress, and prior to depolarization, PINK1 and Parkin mediate a pathway delivering mitochondria-derived vesicles (MDVs), carrying damaged mitochondrial components, directly to endolysosomes. b Under conditions of oxidative stress, Nix and Bnip3 can bind with MIEAP (mitochondrial-eating protein), to induce autophagy-independent interactions of mitochondria with lysosome-like organelles. c Activity of canonical BH3-only proteins, or mitochondrial depolarization, triggers mitochondrial ubiquitylation by the endogenous caspase inhibitor and E3 ligase XIAP and Bax/Bak-mediated entering of XIAP into mitochondria. Mitochondrial activity of XIAP recruits endolysosomal trafficking machinery into mitochondria, leading to the degradation of its inhibitor Smac, thereby reducing the apoptotic potential of mitochondria