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

Okumoto, Kanji; El Shermely, Mahmoud; Natsui, Masanao; Kosako, Hidetaka; Natsuyama, Ryuichi; Marutani, Toshihiro; Fujiki, Yukio · Elife · 2020

basic_science · Level V

Where this comes from

Abstract

Most of peroxisomal matrix proteins including a hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-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 H<sub>2</sub>O<sub>2</sub> in mammalian cells. The H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>. We thus suggest that the H<sub>2</sub>O<sub>2</sub>-induced phosphorylation of Pex14 spatiotemporally regulates peroxisomal import of catalase, functioning in counteracting action against oxidative stress by the increase of cytosolic catalase.

Medical subject headings