The reaction of ATP synthase (F0F1) is the final step in oxidative phosphorylation (OXPHOS). Although OXPHOS has been studied extensively in bacteria, no tissue-specific functions nor bioenergetic disease, such as mitochondrial encephalomyopathy and aging occur in these organisms. Recent developments of the Human Genome Project will become an important factor in the study of mammalian bioenergetics. To elucidate the physiological roles of human F0F1, genes encoding the subunits of F0F1 were sequenced, and their expression in human cells was analyzed. The following results were obtained: A. The roles of the residues in F0F1 are not only to transform the energy of the electrochemical potential (ΔμH+) across the membrane, but also to respond rapidly to the changes in the energy demand by regulating the intramolecular rotation of F0F1 with the ΔμH+ and the inhibitors of the ATPase. B. The roles of the control regions of the F0F1 genes, are to coordinate both mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) depending on the energy demand of the cells, especially in muscle. C. The cause of the age-dependent decline of ATP synthesis has been attributed to the accumulation of mutations in mtDNA. However, the involvement of nDNA in the decline is also important because of telomere shortening in somatic cells, and age-dependent mtDNA expression analyzed with ρ° cells (cells without mtDNA).
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Review Article|
April 01 1997
Genes of Human ATP Synthase: Their Roles in Physiology and Aging
Yasuo Kagawa;
Yasuo Kagawa
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Toshiro Hamamoto;
Toshiro Hamamoto
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Hitoshi Endo;
Hitoshi Endo
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Masaru Ichida;
Masaru Ichida
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Hirobumi Shibui;
Hirobumi Shibui
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Morisada Hayakawa
Morisada Hayakawa
1Department of Biochemistry, Jichi Medical School, Tochigi-ken, 329-04, Japan.
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Publisher: Portland Press Ltd
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 1997 Plenum Publishing Corporation
1997
Biosci Rep (1997) 17 (2): 115–146.
Citation
Yasuo Kagawa, Toshiro Hamamoto, Hitoshi Endo, Masaru Ichida, Hirobumi Shibui, Morisada Hayakawa; Genes of Human ATP Synthase: Their Roles in Physiology and Aging. Biosci Rep 1 April 1997; 17 (2): 115–146. doi: https://doi.org/10.1023/A:1027329328504
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