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

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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.

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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.

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Kanji Okumoto

Faculty of Sciences, Kyushu University, Fukuoka, Japan

Competing interests
No competing interests declared.
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..
Masanao Natsui

Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan

Competing interests
No competing interests declared.
Hidetaka Kosako

Fujii Memorial Institute of Medical Sciences, Tokushima University, Tokushima, Japan

Competing interests
No competing interests declared.
Ryuichi Natsuyama

Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan

Competing interests
No competing interests declared.
Toshihiro Marutani

Faculty of Sciences, Kyushu University, Fukuoka, Japan

Competing interests
No competing interests declared.
Yukio Fujiki

Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan

For correspondence
yfujiki@kyudai.jp

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-8138-6376

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

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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.