title: Targeting the F1Fo ATP Synthase: modulation of the body's powerhouse and its implications for human disease.
abstract: Throughout our lifetime the F1Fo ATP synthase produces the majority of our biological energy, and plays central roles in the structure and organization of mitochondria, yet our understanding of its roles in human disease remain largely enigmatic. It seems logical that even intermittent impairment of this highly important enzyme could deprive the body's tissues of energy at crucial times, which may predispose or contribute to illness. Indeed, evidence is accumulating that there are dire consequences of energy depletion in acute lifethreatening conditions, such as heart attacks, as well as chronic diseases, including aging, cancer, diabetes and heart failure. Recent advances in our understanding of the expanding roles of F1Fo ATP synthase, and how it is regulated, combined with the development of novel strategies for manipulating its function, may provide renewed hope for therapeutic improvement of energy homeostasis, and mitochondrial integrity, in a host of human diseases. In this review we will highlight what is known about the molecular regulation of this amazing enzyme complex, discuss effects of physiological agonists and therapeutic drugs on its functions, and present evidence supporting its involvement in the ills of mankind. Finally, we will outline existing challenges, and promising new avenues for targeting the enzyme therapeutically.
authors.affiliation: The Department of Pharmacology & Toxicology, School of Medicine, and The Program in Regenerative Medicine, Institute of Molecular Medicine and Genetics, Georgia Health Sciences University, Augusta, USA. jjohnson@georgiahealth.edu
authors.forename: J A
authors.initials: JA
authors.lastname: Johnson
authors.forename: Mourad
authors.initials: M
authors.lastname: Ogbi
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000417:Albinism / Q000188:drug therapy; D000437:Alcoholism / Q000503:physiopathology; D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology; D001424:Bacterial Infections / Q000503:physiopathology; D031204:Caloric Restriction; D002318:Cardiovascular Diseases / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000503:physiopathology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000201:enzymology*; D000226:Mitochondrial ADP, ATP Translocases / Q000502:physiology; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D008958:Models, Molecular; D009369:Neoplasms / Q000503:physiopathology; D010085:Oxidative Phosphorylation; D021122:Protein Subunits / Q000737:chemistry
chemical_list: D000305:Adrenal Cortex Hormones; D021122:Protein Subunits; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D025261:Mitochondrial Proton-Translocating ATPases