Mitochondria control both cell’s life and death. To ensure the well-being of the cell, mitochondrial quality and quantity must be tightly monitored through a mechanism of mitochondrial autophagy or mitophagy, which selectively removes damaged or unwanted mitochondria. We recently have identified that mitochondrial outer membrane protein FUNDC1 harbors LC3-interacting region (LIR) and interacts with LC3 to mediate mitophagy in response to mitochondrial stresses and hypoxic treatment. We showed that the interaction between FUNDC1 and LC3 was regulated by reversible phosphorylation, and further identified that Src kinase and CK2 were able to phosphorylate FUNDC1 at Try18 and Ser13, respectively, while mitochondrially localized phosphatase PGAM5 was able to dephosphorylate FUNDC1 at Ser-13 to activate mitophagy. In addition, we found that Bcl-xL, but not Bcl-2, interacted with and inhibited the phosphatase activities of PGAM to block mitophagy. We are currently addressing the question how mitochondrial fission and fusion are coupled with mitophagy and how defective mitophagy is closely linked with aging related diseases using FUNDC1 deficient mice.