PP2A-like protein phosphatase Ppg1: an emerging negative regulator of mitophagy in yeast

Abstract

Macroautophagy/autophagy (bulk autophagy) is a catabolic process that nonselectively degrades cytoplasmic proteins and organelles. In contrast to bulk autophagy, selective types of autophagy target specific cellular components as cargos, whereas their specific receptor proteins play central roles in cargo selection. In the yeast Saccharomyces cerevisiae, receptor proteins for the cytoplasm-to-vacuole targeting pathway, mitophagy, and pexophagy are phosphoregulated by kinases. This phosphorylation facilitates interaction with the scaffold/adaptor protein Atg11, subsequently recruiting core autophagy proteins to initiate autophagosome formation. However, the molecular mechanism inhibiting this phosphorylation to prevent unrequired selective autophagy remains unknown. Our recent study revealed that the protein phosphatase 2A-like protein phosphatase Ppg1 and its associated Far complex cooperatively inhibit mitophagy by counteracting casein kinase 2-mediated phosphorylation of the mitophagy receptor Atg32. Herein, we summarize our findings regarding Ppg1 and pose unanswered questions.

Keywords: Atg32; Far complex; Ppg1; autophagy; casein kinase 2; mitochondria; mitophagy; yeast.

Figure 1.

Model for the regulatory mechanism of Atg32 phosphorylation. Under normal conditions, Ppg1 with the Far complex dephosphorylates Atg32 via its amino acid 151–200 region to prevent unrequired mitophagy. Upon mitophagy induction, the activity of Ppg1 is suppressed through unidentified mechanisms (such as dissociation of Ppg1 and the Far complex and binding of an inhibitory protein to Ppg1), leading to Atg32 phosphorylation by CK2.