FBS Colloquia No.339Laboratory of Mitochondrial Dynamics

Locking and unlocking mechanisms for initiation of selective mitochondrial clearance

Selective autophagy, which mediates sorting and removal of dysfunctional or excess organelles and protein aggregates in cells, is widely conserved across species and plays a crucial role in maintaining cellular homeostasis. In budding yeast, selective mitochondrial degradation, termed mitophagy, is driven by Atg32, a protein that specifically labels mitochondria and binds to Atg11, a scaffold protein commonly important for selective autophagy. Since Atg11 serves to promote core Atg protein assembly that is required for generation of autophagosomal membranes enclosing mitochondria, the Atg32-Atg11 interaction is thought to be a prerequisite for mitophagy initiation. However, the details of these interactions remain unclear. Therefore, by analyzing molecular functions of various Atg32 and Atg11 mutants that were generated using the information on partial structures of the Atg32-Atg11 complex, we sought to elucidate the regulatory mechanisms of mitophagy initiation. In this colloquium, we will present our updated data and discuss the locking and unlocking mechanisms of mitophagy via phosphorylation of Atg32 and Atg11.