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 bodys 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, kinases, mitochondria, oxidative phosphorylation, subunits, physiological agonists, energy homeostasis, mitochondrial integrity, molecular regulation
Current Medicinal Chemistry
Title: Targeting the F1Fo ATP Synthase: Modulation of the Bodys Powerhouse and Its Implications for Human Disease
Volume: 18 Issue: 30
Author(s): John A. Johnson and Mourad Ogbi
Affiliation:
Keywords: Disease, F1Fo ATP synthase, kinases, mitochondria, oxidative phosphorylation, subunits, physiological agonists, energy homeostasis, mitochondrial integrity, molecular regulation
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 bodys 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.
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Cite this article as:
A. Johnson John and Ogbi Mourad, Targeting the F1Fo ATP Synthase: Modulation of the Bodys Powerhouse and Its Implications for Human Disease, Current Medicinal Chemistry 2011; 18 (30) . https://dx.doi.org/10.2174/092986711797379177
DOI https://dx.doi.org/10.2174/092986711797379177 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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