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过氧化物酶体通过磷酸化 Pex14 抑制过氧化氢酶的导入来抵抗氧化应激。

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

机构信息

Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan.

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

出版信息

Elife. 2020 Aug 24;9:e55896. doi: 10.7554/eLife.55896.

DOI:10.7554/eLife.55896
PMID:32831175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7498260/
Abstract

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

摘要

大多数过氧化物酶体基质蛋白，包括过氧化氢 (HO) 分解酶过氧化氢酶，都是以过氧化物酶体靶向信号类型 1 (PTS1) 依赖的方式被输入的。然而，对于膜结合蛋白输入机制的调节却知之甚少。在这里，我们报告说，过氧化物酶体膜中蛋白质易位复合物的核心组成部分 Pex14 会在哺乳动物细胞中受到 HO 等氧化应激的影响而发生磷酸化。HO 诱导的 Pex14 在 Ser232 处的磷酸化会抑制体内过氧化氢酶的过氧化物酶体导入，并选择性地损害过氧化氢酶与 Pex14-Pex5 复合物的体外相互作用。磷酸模拟突变体 Pex14-S232D 会提高细胞质中过氧化氢酶的水平，但不会提高经典 PTS1-蛋白的水平，从而使细胞对 HO 的抗性更高。因此，我们认为 HO 诱导的 Pex14 磷酸化时空调节过氧化氢酶的过氧化物酶体导入，通过增加细胞质中的过氧化氢酶来发挥对抗氧化应激的拮抗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/e1ca2cb87871/elife-55896-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/334fd75bdc54/elife-55896-fig1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/49e5f88455f3/elife-55896-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/c88546efb4e9/elife-55896-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/af822e195ab3/elife-55896-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/5bf4632bd21d/elife-55896-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/47f6cc980dac/elife-55896-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/101fe44113a0/elife-55896-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/47fdfe5c13d8/elife-55896-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/8321bc6ff014/elife-55896-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/5d785e051cc7/elife-55896-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/e1ca2cb87871/elife-55896-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/334fd75bdc54/elife-55896-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/69e103d15562/elife-55896-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/59330e4e722f/elife-55896-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/6f94638539af/elife-55896-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/49e5f88455f3/elife-55896-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/c88546efb4e9/elife-55896-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/af822e195ab3/elife-55896-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/5bf4632bd21d/elife-55896-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/47f6cc980dac/elife-55896-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/101fe44113a0/elife-55896-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/47fdfe5c13d8/elife-55896-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/8321bc6ff014/elife-55896-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/5d785e051cc7/elife-55896-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c496/7498260/e1ca2cb87871/elife-55896-fig6.jpg

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