ATP synthase: from single molecule to human bioenergetics.
ATP synthase (F(o)F(1)) consists of an ATP-driven motor (F(1)) and a H(+)-driven motor (F(o)), which rotate in opposite directions. F(o)F(1) reconstituted into a lipid membrane is capable of ATP synthesis driven by H(+) flux. As the basic structures of F(1) (alpha(3)beta(3)gammadeltaepsilon) and F(o) (ab(2)c(10)) are ubiquitous, stable thermophilic F(o)F(1) (TF(o)F(1)) has been used to elucidate molecular mechanisms, while human F(1)F(o) (HF(1)F(o)) has been used to study biomedical significance. Among F(1)s, only thermophilic F(1) (TF(1)) can be analyzed simultaneously by reconstitution, crystallography, mutagenesis and nanotechnology for torque-driven ATP synthesis using elastic coupling mechanisms. In contrast to the single operon of TF(o)F(1), HF(o)F(1) is encoded by both nuclear DNA with introns and mitochondrial DNA. The regulatory mechanism, tissue specificity and physiopathology of HF(o)F(1) were elucidated by proteomics, RNA interference, cytoplasts and transgenic mice. The ATP synthesized daily by HF(o)F(1) is in the order of tens of kilograms, and is primarily controlled by the brain in response to fluctuations in activity.
Kagawa
Yasuo
Y
Department of Biochemistry, Tochigi, Japan. kagawa@eiyo.ac.jp
D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000502:physiology; D004734:Energy Metabolism; D006801:Humans; D007438:Introns / Q000235:genetics / Q000502:physiology; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D025261:Mitochondrial Proton-Translocating ATPases