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

Kanji Okumoto,Mahmoud El Shermely,Hidetaka Kosako,Ryuichi Natsuyama,Masanao Natsui,Yukio Fujiki,Toshihiro Marutani

doi:10.7554/elife.55896

Kanji Okumoto, Mahmoud El Shermely + Show 5 more

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

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Journal: eLife	Publication Date: Aug 24, 2020
Citations: 45	License type: CC BY 4.0

Affiliation: Kyushu University, Tokushima University

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.

Highlights

Peroxisome, an essential intracellular organelle, functions in various essential metabolism including β-oxidation of very long chain fatty acids, and the synthesis of ether phospholipids (Waterham et al, 2016)
Two topogenic signals are identified in the majority of peroxisomal matrix proteins: peroxisome targeting signal type-1 (PTS1) is a C-terminal tripeptide sequence SKL and its derivatives (Gould et al, 1987; Miura et al, 1992) and PTS2 is an N-terminal cleavable nonapeptide presequence (Osumi et al, 1991; Swinkels et al, 1991)
Of 14 peroxisome assembly factors called peroxins in mammals, Pex[14] is a peroxisomal membrane peroxin playing a central role in the import of both peroxisome-targeting signal type-1 (PTS1)- and PTS2-proteins (reviewed in (Fujiki et al, 2014; Platta et al, 2016)

Summary

Introduction

Peroxisome, an essential intracellular organelle, functions in various essential metabolism including β-oxidation of very long chain fatty acids, and the synthesis of ether phospholipids (Waterham et al, 2016). Peroxisomal functions rely on the tightly and spatiotemporally regulated import of the enzyme proteins responsible for respective reactions. Of 14 peroxisome assembly factors called peroxins in mammals, Pex[14] is a peroxisomal membrane peroxin playing a central role in the import of both PTS1- and PTS2-proteins (reviewed in (Fujiki et al., 2014; Platta et al, 2016). By associating of Pex[5] with the import machinery complexes in peroxisome membrane comprising Pex[14], Pex[13], and RING peroxins Pex[2], Pex[10] and Pex[12], Pex[5] transports its cargo proteins into the matrix, and shuttles back to the cytosol (reviewed in Fujiki et al, 2014; Liu et al, 2012; Platta et al, 2016)

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