title: VCP Is an integral component of a novel feedback mechanism that controls intracellular localization of catalase and H2O2 Levels.
abstract: 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.
authors: Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Sakyo-ku, Kyoto, Japan.
authors: Katsuhiro
authors: K
authors: Murakami
authors: Yuzuru
authors: Y
authors: Ichinohe
authors: Masaaki
authors: M
authors: Koike
authors: Norio
authors: N
authors: Sasaoka
authors: Shun-ichiro
authors: S
authors: Iemura
authors: Tohru
authors: T
authors: Natsume
authors: Akira
authors: A
authors: Kakizuka
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000032:analysis* / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation; D000074405:Valosin Containing Protein
chemical_list: D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C087343:PEX19 protein, human; D006861:Hydrogen Peroxide; D002374:Catalase; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein