Atg43, a novel autophagy-related protein, serves as a mitophagy receptor to bridge mitochondria with phagophores in fission yeast

Abstract

Mitophagy is a selective type of autophagy in which damaged or unnecessary mitochondria are sequestered by double-membranous structures called phagophores and delivered to vacuoles/lysosomes for degradation. The molecular mechanisms underlying mitophagy have been studied extensively in budding yeast and mammalian cells. To gain more diverse insights, our recent study identified Atg43 as a mitophagy receptor in the fission yeast Schizosaccharomyces pombe. Atg43 is localized on the mitochondrial outer membrane through the Mim1-Mim2 complex and binds to Atg8, a ubiquitin-like protein conjugated to phagophore membranes. Artificial tethering of Atg8 to mitochondria can bypass the requirement of Atg43 for mitophagy, suggesting that the main role of Atg43 in mitophagy is to stabilize phagophore expansion on mitochondria by interacting with Atg8. Atg43 shares no sequence similarity with mitophagy receptors in other organisms and has a mitophagy-independent function, raising the possibility that Atg43 has acquired the mitophagic function by convergent evolution.

Keywords: Atg43; Atg8; MIM complex; autophagy; mitochondria; mitophagy; selective autophagy; yeast.

Figure 1.

Atg43 tethers phagophores to the MOM for the efficient engulfment of mitochondria. (A) Schematic representation of the primary structure of Atg43. The C-terminal region that is conserved among fungi is marked. Regions involved in the individual processes are indicated. TM, transmembrane domain. (B) Schematic model for mitophagy promoted by Atg43. The extending phagophore is stabilized on the MOM by the interaction between Atg8 on the phagophore membrane and the N-terminal AIM of Atg43. Atg43 is also involved in an unknown cellular process that facilitates cell growth, possibly with the MIM complex