Kioka, H., Kato, H., Fujikawa, M., Tsukamoto, O., Suzuki, T., Imamura, H., … Takashima, S.
Departments of Medical Biochemistry and Cardiovascular Medicine and Centre for Research Education, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan, Department of Biochemistry, Faculty of Pharmaceutical Science, Tokyo University of Science, Chiba 278-8510, Japan, Chemical Resources Laboratory, Tokyo Institute of Technology, Yokohama 226-8503, Japan, Department of Molecular Bioscience, Kyoto Sangyo University, Kyoto
603-8555, Japan, The Hakubi Centre for Advanced Research and Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan, Departments of Clinical Research and Development and Cell Biology, National Cerebral and Cardiovascular Centre Research Institute, Osaka 565-8565, Japan, Department of Cardiovascular Science and Technology, Kyoto Prefectural University School of Medicine, Kyoto 602-8566, Japan, and Department of Applied Chemistry, School of Engineering and Department of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo, Tokyo 113-8656, Japan.
The oxidative phosphorylation (OXPHOS) system generates most of the ATP in respiring cells. ATP-depleting conditions, such as hypoxia, trigger responses that promote ATP production. However, how OXPHOS is regulated during hypoxia has yet to be elucidated. In this study, selective measurement of intramitochondrial ATP levels identified the hypoxia-inducible protein G0/G1 switch gene 2 (G0s2) as a positive regulator of OXPHOS. A mitochondria-targeted, FRET-based ATP biosensor enabled us to assess OXPHOS activity in living cells. Mitochondria-targeted, FRET-based ATP biosensor and ATP production assay in a semiintact cell system revealed that G0s2 increases mitochondrial ATP production. The expression of G0s2 was rapidly and transiently induced by hypoxic stimuli, and G0s2 interacts with OXPHOS complex V (FoF1-ATP synthase). Furthermore, physiological enhancement of G0s2 expression prevented cells from ATP depletion and induced a cellular tolerance for hypoxic stress. These results show that G0s2 positively regulates OXPHOS activity by interacting with FoF1-ATP synthase, which causes an increase in ATP production in response to hypoxic stress and protects cells from a critical energy crisis. These findings contribute to the understanding of a unique stress response to energy depletion. Additionally, this study shows the importance of assessing intramitochondrial ATP levels to evaluate OXPHOS activity in living cells.
… “Cells were illuminated using the CoolLED pE-1 excitation system (CoolLED) with a wavelength of 425 nm.”…
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pE-2: A repeatable, controllable modular system with 20 different LED peaks. Instant on/off and intensity (0-100%) control.
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