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.

Tripartite suppression of fission yeast TORC1 signaling by the GATOR1-Sea3 complex, the TSC complex, and Gcn2 kinase

“…Aiming to evaluate the physiological roles of these negative regulatory mechanisms toward TORC1 activity, we turned our attention to autophagy, which is induced by TORC1 inactivation during nutritional starvation ( Kohda et al, 2007 ). Autophagic degradation of GFP-tagged phosphoglycerate kinase (Pgk1) has been successfully used as a quantitative readout of autophagy ( Welter et al, 2010 ; Fukuda et al, 2020 ); upon autophagy induction, Pgk1-GFP is transported from the cytoplasm to vacuoles for degradation, but the GFP moiety remains undigested due to its resistance to the vacuolar proteases. Thus, the cellular autophagic activity in response to starvation can be monitored by immunoblotting to detect the free GFP released from Pgk1-GFP ( Figure 4—figure supplement 1A ).…”

Plant Mitophagy in Comparison to Mammals: What Is Still Missing?

“…However, it remains unknown whether the ATG32–ATG11 complex promotes mitochondrial fission by interacting with DNM1. Differently, in fission yeast, it has been found that another OMM protein, named ATG43, might function as a mitophagy receptor by coordinating with the mitochondrial import factors instead [ 46 ].…”

“…( B ) In budding yeast, the only identified receptor is ATG32, which is phosphorylated and recognized by ATG11 or ATG8 respectively [ 42 , 43 , 44 , 45 ]. Another mitochondrial outer membrane protein, ATG43, serves as the mitophagy receptor in fission yeast [ 46 ]. However, the function of cardiolipin is not clear in yeast mitophagy.…”

Mitophagy in Yeast: Decades of Research

“…As in S. cerevisiae , nitrogen starvation induced autophagic elimination of mitochondria in this fission yeast, but the molecular mechanism underlying this degradation, and whether this pathway is selective to mitochondria, remains uncertain [ 93 , 94 ]. In their recent work, Fukuda et al (2020) identified the protein Atg43 as a new mitophagy receptor in S. pombe [ 95 ].…”