The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy

Citations Over TimeTop 10% of 2014 papers

Abstract

Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial quality control essential for cell survival. We previously have identified FUNDC1 as a mitophagy receptor for selectively removing damaged mitochondria in mammalian systems. A critical unanswered question is how receptor-mediated mitophagy is regulated in response to cellular and environmental cues. Here, we report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated mitophagy in response to hypoxia and that BCL2L1 possesses unique functions distinct from BCL2.

Related Papers

• → A Mammalian Mitophagy Receptor, Bcl2-L-13, Recruits the ULK1 Complex to Induce Mitophagy(2019)156 cited
• → Molecular signaling toward mitophagy and its physiological significance(2013)95 cited
• → [Research progress on mechanism of Nix-mediated mitophagy].(2017)5 cited
• → Phosphorylation Events in Selective Mitophagy: Possible Biochemical Markers?(2013)2 cited
• → FBXL4 suppresses mitophagy by restricting the accumulation of NIX and BNIP3 mitophagy receptors(2022)9 cited