Abstract

Mitochondria-targeted selective autophagy, termed mitophagy, is an evolutionarily conserved process that contributes to mitochondrial quantity and quality control. Mitophagy requires elaborate membrane biogenesis of autophagosomes surrounding mitochondria, although how this process is regulated remains obscure. We show here that mitophagy is strongly suppressed in yeast cells lacking Nem1 or Spo7, two proteins forming a heterodimeric protein phosphatase complex known to be important for proper shaping of the nucleus and endoplasmic reticulum (ER). Under the same conditions, selective degradation of the ER and peroxisomes was also suppressed strongly and to a lesser extent, respectively, whereas autophagy and the cytoplasm to vacuole targeting (Cvt) pathway were only slightly affected in those mutants. We also found that mitochondrial sequestration in the cytoplasm and their degradation in the vacuole, a lytic compartment in yeast, occurred poorly but did not completely arrest. Notably, deletion of the INO2 gene in the nem1-or spo7-null mutant partially rescued nuclear/ER membrane shaping and mitophagy. Together, our data suggest that Nem1-Sop7-mediated regulation of membrane biogenesis is needed to promote mitophagy in yeast.

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