The ER membrane insertase Get1/2 complex is required for efficient mitophagy in yeast Mashun Onishi1, Sachiyo Nagumo1, Koji Okamoto1* 1Graduate School of Frontier Biosciences, Osaka University *Corresponding Author
Mitophagy is an evolutionarily conserved autophagy pathway that selectively eliminates mitochondria to control mitochondrial quality and quantity. Although mitophagy is thought to be essential for cellular homeostasis, how this catabolic process is regulated remains largely unknown. Here we demonstrate that mitophagy during prolonged respiratory growth is strongly impaired in yeast cells lacking Get1/2, a transmembrane complex mediating insertion of tail-anchored (TA) proteins into the endoplasmic reticulum (ER) membrane. Under the same conditions, loss of Get1/2 caused only slight defects in other types of selective organellophagy (ER and peroxisome degradation) and bulk autophagy. Previous studies revealed that ER targeting of TA proteins and mitochondrial morphology are substantially disrupted in the absence of Get1/2. Notably, mitophagy and other autophagy-related processes are mostly normal in cells lacking Get3, a cytosolic ATP-driven chaperone that promotes delivery of TA proteins to the Get1/2 complex. We also found that Get1/2-deficient cells exhibited wildtype-like mitochondrial fragmentation during mitophagy. Collectively, we propose that Get1/2-dependent TA protein(s) and/or the Get1/2 complex itself may act specifically in mitophagy.