Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation.
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.
['Kioka|Hidetaka|H|', 'Kato|Hisakazu|H|', 'Fujikawa|Makoto|M|', 'Tsukamoto|Osamu|O|', 'Suzuki|Toshiharu|T|', 'Imamura|Hiromi|H|', 'Nakano|Atsushi|A|', 'Higo|Shuichiro|S|', 'Yamazaki|Satoru|S|', 'Matsuzaki|Takashi|T|', 'Takafuji|Kazuaki|K|', 'Asanuma|Hiroshi|H|', 'Asakura|Masanori|M|', 'Minamino|Tetsuo|T|', 'Shintani|Yasunori|Y|', 'Yoshida|Masasuke|M|', 'Noji|Hiroyuki|H|', 'Kitakaze|Masafumi|M|', 'Komuro|Issei|I|', 'Asano|Yoshihiro|Y|', 'Takashima|Seiji|S|']
D000255:Adenosine Triphosphate D000818:Animals D015374:Biosensing Techniques D002417:Cattle D018797:Cell Cycle Proteins D002470:Cell Survival D016193:G1 Phase D005812:Genes, Switch D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D051379:Mice D018613:Microscopy, Confocal D008928:Mitochondria D032383:Myocytes, Cardiac D009840:Oligomycins D020411:Oligonucleotide Array Sequence Analysis D010085:Oxidative Phosphorylation D010101:Oxygen Consumption D010766:Phosphorylation D051381:Rats D017208:Rats, Wistar D011994:Recombinant Proteins D016192:Resting Phase, Cell Cycle D013997:Time Factors
energy metabolism live-cell imaging