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Targeting the F1Fo ATP Synthase: Modulation of the Body's Powerhouse and Its Implications for Human Disease

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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.

Keywords: Disease; F1Fo ATP synthase; energy homeostasis; kinases; mitochondria; mitochondrial integrity; molecular regulation; oxidative phosphorylation; physiological agonists; subunits

Document Type: Research Article


Publication date: October 1, 2011

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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