Phosphorylation Events in Selective Mitophagy: Possible Biochemical Markers?

Mitophagy, or mitochondrial autophagy, plays an important role in mitochondrial quality control for the selective removal of damaged or unwanted mitochondria. Several molecules, including Parkin, p62 and the mitophagy receptors ATG32, NIX/BNIP3 and FUNDC1, were found to participate selective mitophagy. One critical question is how mitochondrial damage-related signals are sensed and transduced to activate mitophagy. It is emerging that mitophagy is highly regulated by reversible protein phosphorylation. Several kinases were found to be involved in selective mitophagy. Pink1 can phosphorylate Parkin to facilitate the subsequent activation of mitophagy. Casein kinase 2 was found to phosphorylate ATG32 in yeast to promote mitophagy. In contrast, Src kinase phosphorylates FUNDC1 to prevent its interaction with LC3, and the dephosphorylation of FUNDC1 is correlated with the activation of mitophagy in mammalian cells in response to hypoxia. Here, we focus on recent advances in our understanding of the signaling events that activate mitophagy and the implications of these events in diseases. We further suggest the possibility that the phosphorylation status of mitophagy receptors may serve as a biochemical marker of this critical process.