Peroxin Pex14p is the key component for coordinated autophagic degradation of mammalian peroxisomes by direct binding

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Li Jiang1, Sayuri Hara-Kuge, Shun-Ichi Yamashita

  • 1Graduate School of Systems Life Sciences, Faculty of Sciences, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, 812-8581, Japan.

Genes to Cells : Devoted to Molecular & Cellular Mechanisms
|November 1, 2014
PubMed

Insights

Pexophagy, the degradation of peroxisomes, involves Pex14p interacting with LC3-II during starvation. This interaction is regulated by Pex5p, highlighting Pex14p

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Autophagy Research

Background:

  • Pexophagy, the autophagic degradation of peroxisomes, can be induced by serum removal in mammalian cells.
  • Pex14p, a peroxisomal membrane protein, is crucial for peroxisome import and degradation.
  • The interaction between Pex14p and LC3-II (a form of LC3) during starvation is known but mechanistically unclear.

Purpose of the Study:

  • To elucidate the molecular mechanism of the Pex14p-LC3-II interaction.
  • To determine if Pex14p directly binds to LC3-II.
  • To investigate the role of Pex5p in regulating the Pex14p-LC3-II interaction under different nutrient conditions.

Main Methods:

  • Reconstitution of an in vitro conjugation system for LC3-II synthesis.
  • In vitro binding assays to study Pex14p and LC3-II interaction.
  • Analysis of Pex5p-Pex14p interaction using a Pex5p mutant defective in PTS1-protein import.

Main Results:

  • Pex14p directly interacts with LC3-II through its transmembrane domain.
  • Pex5p competitively inhibits the Pex14p-LC3-II interaction, indicating Pex14p prefers Pex5p in nutrient-rich conditions.
  • A Pex5p mutant impaired in PTS1 import shows reduced affinity for Pex14p during nutrient deprivation, favoring Pex14p-LC3-II binding.

Conclusions:

  • Pex14p directly binds LC3-II, mediating peroxisome degradation during starvation.
  • Pex5p acts as a regulator, modulating Pex14p's interaction with LC3-II based on nutrient availability.
  • Pex14p is a key factor in both peroxisomal biogenesis and degradation, adapting to environmental changes via Pex5p coordination.

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