title: Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation.
abstract: 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.
authors.affiliation: Departments of Medical Biochemistry and Cardiovascular Medicine and Center for Research Education, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kioka
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Kato
authors.forename: Makoto
authors.initials: M
authors.lastname: Fujikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Tsukamoto
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiromi
authors.initials: H
authors.lastname: Imamura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Higo
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsuzaki
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Takafuji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shintani
authors.forename: Masasuke
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Noji
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D000818:Animals; D015374:Biosensing Techniques; D002417:Cattle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002470:Cell Survival; D016193:G1 Phase; D005812:Genes, Switch; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology; D009840:Oligomycins / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; C508073:G0S2 protein, human; C508072:G0S2 protein, mouse; C586945:G0S2 protein, rat; D009840:Oligomycins; D011994:Recombinant Proteins; C031004:oligomycin A; D000255:Adenosine Triphosphate
keywords: energy metabolism; live-cell imaging