VCP Is an Integral Component of a Novel Feedback Mechanism that Controls Intracellular Localization of Catalase and H.sub.2O.sub.2 Levels

• Published in: PloS one Vol. 8; no. 2; p. e56012
• Main Authors: Murakami, Katsuhiro, Ichinohe, Yuzuru, Koike, Masaaki, Sasaoka, Norio, Iemura, Shun-ichiro, Natsume, Tohru, Kakizuka, Akira
• Format: Journal Article
• Language: English
• Published: Public Library of Science 14.02.2013
• Subjects: ATPases; Proteolysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056012

Catalase is a key antioxidant enzyme that catalyzes the decomposition of hydrogen peroxide (H.sub.2 O.sub.2) 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 H.sub.2 O.sub.2 -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 H.sub.2 O.sub.2 levels, and regulates them by controlling the localization of catalase.