title: The Degradation Pathway of the Mitophagy Receptor Atg32 Is Re-Routed by a Posttranslational Modification.
abstract: The outer mitochondrial membrane protein Atg32 is the central receptor for mitophagy, the mitochondria-specific form of autophagy. Atg32 is an unstable protein, and is rapidly degraded under conditions in which mitophagy is not induced. Here we show that Atg32 undergoes a posttranslational modification upon induction of mitophagy. The modification is dependent on the core autophagic machinery, including Atg8, and on the mitophagy-specific adaptor protein Atg11. The modified Atg32 is targeted to the vacuole where it becomes stabilized when vacuolar proteases are deficient. Interestingly, we find that this degradation pathway differs from the degradation pathway of non-modified Atg32, which neither involves vacuolar proteases, nor the proteasome. These analyses reveal that a posttranslational modification discriminates a form of Atg32 targeting mitochondria for mitophagy from that, which escapes mitophagy by rapid degradation.
authors.affiliation: Department of Cellular Biochemistry, Georg-August University, Göttingen, Germany.
authors.forename: Mariia
authors.initials: M
authors.lastname: Levchenko
authors.affiliation: Department of Cellular Biochemistry, Georg-August University, Göttingen, Germany.
authors.forename: Isotta
authors.initials: I
authors.lastname: Lorenzi
authors.affiliation: Department of Cellular Biochemistry, Georg-August University, Göttingen, Germany.
authors.forename: Jan
authors.identifier: http://orcid.org/0000-0002-5672-7458
authors.initials: J
authors.lastname: Dudek
mesh_terms: D001343:Autophagy; D000071190:Autophagy-Related Protein 8 Family / Q000378:metabolism; D000071183:Autophagy-Related Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D063306:Mitophagy; D011499:Protein Processing, Post-Translational; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: C113757:ATG8 protein, S cerevisiae; C502923:Atg11 protein, S cerevisiae; C543183:Atg32 protein, S cerevisiae; D000071190:Autophagy-Related Protein 8 Family; D000071183:Autophagy-Related Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins