Mitochondria control both the life and death of a cell.To ensure the well-being of the cell,mitochondrial quality and quantity is tightly monitored through a mechanism called mitophagy,which selectively removes damaged or unwanted mitochondria.We recently identified that the mitochondrial outer membrane protein FUNDC1 harbors a LC3-interacting region (LIR) and interacts with LC3 to mediate mitophagy upon hypoxic conditions.Under normal conditions,FUNDC1 is highly phosphorylated by Sre kinase and CK2 at Tyr18 and Ser13,respectively,to block its interaction with LC3.Under hypoxic or mitochondrial stress conditions,FUNDC 1 becomes dephosphorylated partly through the mitochondrially localized phosphatase PGAM5,thus enhancing its interaction with LC3 to promote mitophagy.Structural analysis further reinforces the notion that reversible phosphorylation serves as the molecular switch for activation of mitophagy.We are currently addressing the (patho-) physiological roles of FUNDC1 in mitochondrial quality control and mitochondrial homeostasis in vivo.