Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit
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概要
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Complex II (succinate-ubiquinone reductase; SQR) is a mitochondrial respiratory chain enzyme that is directly involved in the TCA cycle. Complex II exerts a reverse reaction, fumarate reductase (FRD) activity, in various species such as bacteria, parasitic helminths and shellfish, but the existence of FRD activity in humans has not been previously reported. Here, we describe the detection of FRD activity in human cancer cells. The activity level was low, but distinct, and it increased significantly when the cells were cultured under hypoxic and glucose-deprived conditions. Treatment with phosphatase caused the dephosphorylation of flavoprotein subunit (Fp) with a concomitant increase in SQR activity, whereas FRD activity decreased. On the other hand, treatment with protein kinase caused an increase in FRD activity and a decrease in SQR activity. These data suggest that modification of the Fp subunit regulates both the SQR and FRD activities of complex II and that the phosphorylation of Fp might be important for maintaining mitochondrial energy metabolism within the tumor microenvironment.(Communicated by Takashi SUGIMURA, M.J.A.)
- 日本学士院の論文
著者
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KITA Kiyoshi
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo
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Kita Kiyoshi
Department Of Biomedical Chemistry Graduate School Of Medicine The University Of Tokyo
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ESUMI Hiroyasu
Cancer Physiology Project, Research Center for Innovative Oncology, National Cancer Center Hospital
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Esumi Hiroyasu
Cancer Physiology Project National Cancer Center Hospital East
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TOMITSUKA Eriko
Cancer Physiology Project, Investigative Treatment Division, National Cancer Center Research Institu
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ESUMI Hiroyasu
Cancer Physiology Project, Investigative Treatment Division, National Cancer Center Research Institute East
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