Deficiency of the exportomer components Pex1, Pex6, and Pex15 causes enhanced pexophagy in Saccharomyces cerevisiae

Autophagy. 2014 May;10(5):835-45. doi: 10.4161/auto.28259. Epub 2014 Mar 18.

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.

Keywords: Atg36; Pex1; Pex6; exportomer; peroxin; peroxisome; pexophagy; selective autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adenosine Triphosphatases / genetics*
  • Autophagy / genetics*
  • Autophagy-Related Proteins
  • Intracellular Membranes / metabolism
  • Membrane Proteins / genetics*
  • Organisms, Genetically Modified
  • Peroxisomes / genetics
  • Peroxisomes / metabolism*
  • Phosphoproteins / genetics*
  • Protein Transport / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / physiology*
  • Saccharomyces cerevisiae / ultrastructure
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / physiology
  • Ubiquitinated Proteins / metabolism

Substances

  • ATG36 protein, S cerevisiae
  • Autophagy-Related Proteins
  • Membrane Proteins
  • PEX15 protein, S cerevisiae
  • Phosphoproteins
  • Saccharomyces cerevisiae Proteins
  • Ubiquitinated Proteins
  • Adenosine Triphosphatases
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, S cerevisiae
  • PEX6 protein, S cerevisiae