RT Journal Article
SR Electronic
T1 The GET pathway serves to activate Atg32-mediated mitophagy by ER targeting of the Ppg1-Far complex
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201640
DO 10.26508/lsa.202201640
VO 6
IS 4
A1 Mashun Onishi
A1 Mitsutaka Kubota
A1 Lan Duan
A1 Yuan Tian
A1 Koji Okamoto
YR 2023
UL https://www.life-science-alliance.org/content/6/4/e202201640.abstract
AB 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.