Regulatory mechanisms of mitochondria-specific autophagy via the TORC1 signaling pathway

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I mainly worked on the molecular mechanisms underlying mitophagy initiation in yeast this year. Based on an Atg32-Atg11 interaction assay for cells lacking core Atg proteins, Atg1 is the sole core Atg protein critical for efficient mitophagy initiation under respiratory conditions. I also found that Atg1 acts in Atg32 phosphorylation. Atg32 can be phosphorylated by purified Atg1 in an in vitro phosphorylation assay, raising the high possibility that Atg1 directly phosphorylates Atg32 during mitophagy induction. Expression of an Atg1 variant defective in Atg1-Atg8 and Atg1-Atg11 interactions reduced Atg32 phosphorylation and mitophagy, suggesting that Atg8 and Atg11 serve to recruit Atg1 to the mitophagy initiation complex. Also, Atg1 can be co-immunoprecipitated with Atg32, which is significantly suppressed in cells lacking Atg8 and Atg11, indicating Atg1 targeted mitochondria via its interactions with Atg8 and Atg11. Notably, these defects were restored by deletion of Ppg1, a protein phosphatase that negatively regulates Atg32-mediated mitophagy. Taken together, Atg1 could serve as the direct kinase for Atg32 phosphorylation and is critical for mitophagy induction in yeast under respiratory conditions.