Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast

Abstract
Degradation of mitochondria through mitophagy contributes to the maintenance of mitochondrial function. In this study, we identified that Atg43, a mitochondrial outer membrane protein, serves as a mitophagy receptor in the model organism Schizosaccharomyces pombe to promote the selective degradation of mitochondria. Atg43 contains an Atg8-family-interacting motif essential for mitophagy. Forced recruitment of Atg8 to mitochondria restores mitophagy in Atg43-deficient cells, suggesting that Atg43 tethers expanding isolation membranes to mitochondria. We found that the mitochondrial import factors, including the Mim1–Mim2 complex and Tom70, are crucial for mitophagy. Artificial mitochondrial loading of Atg43 bypasses the requirement of the import factors, suggesting that they contribute to mitophagy through Atg43. Atg43 not only maintains growth ability during starvation but also facilitates vegetative growth through its mitophagy-independent function. Thus, Atg43 is a useful model to study the mechanism and physiological roles, as well as the origin and evolution, of mitophagy in eukaryotes.
Funding Information
  • Japan Society for the Promotion of Science (17K07330)
  • Japan Society for the Promotion of Science (20K06552)
  • Takeda Science Foundation
  • Japan Society for the Promotion of Science (18H04858)
  • Japan Society for the Promotion of Science (19H05712)
  • Japan Society for the Promotion of Science (19K22419)
  • Japan Agency for Medical Research and Development (20gm6110013h0003)