BAG6 promotes PINK1 signaling pathway and is essential for mitophagy

Bcl-2-associated athanogen-6 (BAG6) is a nucleocytoplasmic shuttling protein involved in quality control. We previously demonstrated that BAG6 essential for autophagy by regulating the intracellular localization of acetyltransferase EP300, and thus, modifying accessibility to its substrates (TP53 nucleus autophagy-related proteins cytoplasm). Here, we investigated function cytoplasm. First, localized mitochondria. Specifically, expressed mitochondrial matrix under basal conditions, translocates outer membrane after depolarization with carbonyl cyanide m-chlorophenyl hydrazine, uncoupler induces mitophagy. In SW480 cells, deletion expression abrogates ability induce mitophagy PINK1 accumulation. On reverse, ectopic LoVo colon cancer which do not express endogenous BAG6, reduces size mitochondria, mitophagy, leads activation PINK1/PARKIN pathway phospho-ubiquitination proteins. Finally, contains two LIR (LC3-interacting Region) domains specifically found receptors selective responsible interaction LC3 autophagosome selectivity. Site-directed mutagenesis showed requires wild-type LIRs stimulate conclusion, propose novel receptor or adaptor signaling LIR-dependent manner.