title: Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae.
abstract: Turnover of damaged, dysfunctional, or excess organelles is critical to cellular homeostasis. We screened mutants disturbed in peroxisomal protein import, and found that a deficiency in the exportomer subunits Pex1, Pex6, and Pex15 results in enhanced turnover of peroxisomal membrane structures compared with other mutants. Strikingly, almost all peroxisomal membranes were associated with phagophore assembly sites in pex1Δ atg1Δ cells. Degradation depended on Atg11 and the pexophagy receptor Atg36, which mediates degradation of superfluous peroxisomes. Mutants of PEX1, PEX6, and PEX15 accumulate ubiquitinated receptors at the peroxisomal membrane. This accumulation has been suggested to trigger pexophagy in mammalian cells. We show by genetic analysis that preventing this accumulation does not abolish pexophagy in Saccharomyces cerevisiae. We find Atg36 is modified in pex1Δ cells even when Atg11 binding is prevented, suggesting Atg36 modification is an early event in the degradation of dysfunctional peroxisomal structures in pex1Δ cells via pexophagy.
authors.affiliation: Department of Molecular Biology and Biotechnology; University of Sheffield, Western Bank; Sheffield, UK.
authors.forename: James M
authors.initials: JM
authors.lastname: Nuttall
authors.affiliation: Department of Molecular Biology and Biotechnology; University of Sheffield, Western Bank; Sheffield, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Motley
authors.affiliation: Department of Molecular Biology and Biotechnology; University of Sheffield, Western Bank; Sheffield, UK.
authors.forename: Ewald H
authors.initials: EH
authors.lastname: Hettema
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D001343:Autophagy / Q000235:genetics*; D000071183:Autophagy-Related Proteins; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D030781:Organisms, Genetically Modified; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics*; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: C523512:ATG36 protein, S cerevisiae; D000071183:Autophagy-Related Proteins; D008565:Membrane Proteins; C110177:PEX15 protein, S cerevisiae; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D057149:Ubiquitinated Proteins; D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C511586:PEX1 protein, S cerevisiae; C490760:PEX6 protein, S cerevisiae
keywords: Atg36; Pex1; Pex6; exportomer; peroxin; peroxisome; pexophagy; selective autophagy