The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation

Abstract

Most of peroxisomal matrix proteins including a hydrogen peroxide (H2O2)-decomposing enzyme, catalase, are imported in a peroxisome-targeting signal type-1 (PTS1)-dependent manner. However, little is known about regulation of the membrane-bound protein import machinery. Here, we report that Pex14, a central component of the protein translocation complex in peroxisomal membrane, is phosphorylated in response to oxidative stresses such as H2O2 in mammalian cells. The H2O2-induced phosphorylation of Pex14 at Ser232 suppresses peroxisomal import of catalase in vivo and selectively impairs in vitro the interaction of catalase with the Pex14-Pex5 complex. A phosphomimetic mutant Pex14-S232D elevates the level of cytosolic catalase, but not canonical PTS1-proteins, conferring higher cell resistance to H2O2. We thus suggest that the H2O2-induced phosphorylation of Pex14 spatiotemporally regulates peroxisomal import of catalase, functioning in counteracting action against oxidative stress by the increase of cytosolic catalase.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files. Source data files have been provided for Figures 2, 3, 4, and 6.

Article and author information

Author details

  1. Kanji Okumoto

    Faculty of Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    No competing interests declared.
  2. Mahmoud El Shermely

    Faculty of Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    Mahmoud El Shermely, Mahmoud El Shermely is affiliated with Basilea Pharmaceutica International Ltd.. The author has no financial interests to declare..
  3. Masanao Natsui

    Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    No competing interests declared.
  4. Hidetaka Kosako

    Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan
    Competing interests
    No competing interests declared.
  5. Ryuichi Natsuyama

    Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    No competing interests declared.
  6. Toshihiro Marutani

    Faculty of Sciences, Kyushu University, Fukuoka, Japan
    Competing interests
    No competing interests declared.
  7. Yukio Fujiki

    Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    For correspondence
    yfujiki@kyudai.jp
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8138-6376

Funding

The authors declare that there was no funding for this work.

Reviewing Editor

  1. Ramanujan S Hegde, MRC Laboratory of Molecular Biology, United Kingdom

Version history

  1. Received: February 10, 2020
  2. Accepted: August 24, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. Version of Record published: September 17, 2020 (version 2)

Copyright

© 2020, Okumoto et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Kanji Okumoto
  2. Mahmoud El Shermely
  3. Masanao Natsui
  4. Hidetaka Kosako
  5. Ryuichi Natsuyama
  6. Toshihiro Marutani
  7. Yukio Fujiki
(2020)
The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation
eLife 9:e55896.
https://doi.org/10.7554/eLife.55896

Share this article

https://doi.org/10.7554/eLife.55896

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