@article {Onishie202201640, author = {Mashun Onishi and Mitsutaka Kubota and Lan Duan and Yuan Tian and Koji Okamoto}, title = {The GET pathway serves to activate Atg32-mediated mitophagy by ER targeting of the Ppg1-Far complex}, volume = {6}, number = {4}, elocation-id = {e202201640}, year = {2023}, doi = {10.26508/lsa.202201640}, publisher = {Life Science Alliance}, abstract = {Mitophagy removes defective or superfluous mitochondria via selective autophagy. In yeast, the pro-mitophagic protein Atg32 localizes to the mitochondrial surface and interacts with the scaffold protein Atg11 to promote degradation of mitochondria. Although Atg32-Atg11 interactions are thought to be stabilized by Atg32 phosphorylation, how this posttranslational modification is regulated remains obscure. Here, we show that cells lacking the guided entry of the tail-anchored protein (GET) pathway exhibit reduced Atg32 phosphorylation and Atg32-Atg11 interactions, which can be rescued by additional loss of the ER-resident Ppg1-Far complex, a multi-subunit phosphatase negatively acting in mitophagy. In GET-deficient cells, Ppg1-Far is predominantly localized to mitochondria. An artificial ER anchoring of Ppg1-Far in GET-deficient cells significantly ameliorates defects in Atg32-Atg11 interactions and mitophagy. Moreover, disruption of GET and Msp1, an AAA-ATPase that extracts non-mitochondrial proteins localized to the mitochondrial surface, elicits synthetic defects in mitophagy. Collectively, we propose that the GET pathway mediates ER targeting of Ppg1-Far, thereby preventing dysregulated suppression of mitophagy activation.}, URL = {https://www.life-science-alliance.org/content/6/4/e202201640}, eprint = {https://www.life-science-alliance.org/content/6/4/e202201640.full.pdf}, journal = {Life Science Alliance} }