VCP Is an integral component of a novel feedback mechanism that controls intracellular localization of catalase and H2O2 Levels.

VCP Is an integral component of a novel feedback mechanism that controls intracellular localization of catalase and H2O2 Levels.
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DOI:
10.1371/journal.pone.0056012
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Kakizuka A
Kakizuka A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Murakami K;Ichinohe Y;Koike M;Sasaoka N;Iemura S;Natsume T;Kakizuka A

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过氧化氢酶是一种关键的抗氧化酶,它催化过氧化氢分解成水和氧,它似乎通过未知的机制在细胞质和过氧化物体之间穿梭。Valosin-Holding Protein(VCP)属于ATPase的AAA类,参与细胞周期和蛋白质降解等多种细胞功能。VCP或PEX19的敲除导致过氧化氢酶主要分布在胞质,VCP ATPase活性的丧失也增加了其胞浆重分布。此外,在正常和过氧化氢处理的细胞中,VCP基因敲除降低了细胞内的ROS水平,而抗氧化的VCP削弱了ROS诱导的过氧化氢酶在细胞质中的重新分布。这些观察揭示了一种新的反馈机制,其中VCP可以感知H_2O_2水平,并通过控制过氧化氢酶的定位来调节它们。
Catalase is a key antioxidant enzyme that catalyzes the decomposition of hydrogen peroxide (H2O2) to water and oxygen, and it appears to shuttle between the cytoplasm and peroxisome via unknown mechanisms. Valosin-containing protein (VCP) belongs to the AAA class of ATPases and is involved in diverse cellular functions, e.g. cell cycle and protein degradation, etc. Here we show that VCP and PEX19, a protein essential for peroxisome biogenesis, interact with each other. Knockdown of either VCP or PEX19 resulted in a predominantly cytoplasmic redistribution of catalase, and loss of VCP ATPase activity also increased its cytoplasmic redistribution. Moreover, VCP knockdown decreased intracellular ROS levels in normal and H2O2-treated cells, and an oxidation-resistant VCP impaired the ROS-induced cytoplasmic redistribution of catalase. These observations reveal a novel feedback mechanism, in which VCP can sense H2O2 levels, and regulates them by controlling the localization of catalase.
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