UC San Diego

Organisms must find a way to degrade and recycle cytoplasmic contents and eliminate redundant organelles. Peroxisomes and mitochondria undergo rapid, targeted degradation in eukaryotic cells by the tightly-regulated pathways of pexophagy and mitophagy, respectively, when they become redundant, damaged, or when the cell experiences starvation or stressful conditions. As classical selective autophagy receptors, Atg19 (yeast receptor for the cytosol to vacuole targeting pathway) and Atg32 (yeast mitophagy receptor) interact with the autophagy-related proteins, Atg8 and Atg11. We identified a novel Atg8-family interacting motif (AIM) of the Saccharomyces cerevisiae pexophagy receptor, Atg36, that is required for its interaction with Atg8. We also found that both Atg32 and Atg36 contain phospho-regulated sites that are required for their interactions with Atg8 and Atg11. Each Atg36 molecule must interact with both Atg8 and Atg11 in order to be fully functional in mediating pexophagy. In this work, we present a common model for the phosphoregulation of selective autophagy receptors. Furthermore, we demonstrated that the kinase, Slt2, previously known to regulate selective autophagy pathways, plays a key role in the phosphorylation of both Atg32 and Atg36. This discovery has led to a deeper understanding of the signaling, regulation, and molecular mechanisms of selective autophagy pathways that may apply to how these processes occur in higher eukaryotes