TY - JOUR TI - The peroxisome counteracts oxidative stresses by suppressing catalase import via Pex14 phosphorylation AU - Okumoto, Kanji AU - El Shermely, Mahmoud AU - Natsui, Masanao AU - Kosako, Hidetaka AU - Natsuyama, Ryuichi AU - Marutani, Toshihiro AU - Fujiki, Yukio A2 - Hegde, Ramanujan S A2 - Ron, David VL - 9 PY - 2020 DA - 2020/08/24 SP - e55896 C1 - eLife 2020;9:e55896 DO - 10.7554/eLife.55896 UR - https://doi.org/10.7554/eLife.55896 AB - 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. KW - catalase KW - Pex14 KW - peroxisomal protein import KW - phosphorylation KW - hydrogen peroxide KW - oxidative stress JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -