The efficiency of cellular energy transduction and its implications for obesity.
We assess the existence, mechanism, and functions of less-than-maximal coupling efficiency of mitochondrial oxidative phosphorylation and its potential as a target for future antiobesity interventions. Coupling efficiency is the proportion of oxygen consumption used to make adenosine triphosphate (ATP) and do useful work. High coupling efficiency may lead to fat deposition; low coupling efficiency to a decrease in fat stores. We review obligatory and facultative energy expenditure and the role of a futile cycle of proton pumping and proton leak across the mitochondrial inner membrane in dissipating energy. Basal proton conductance is catalyzed primarily by the adenine nucleotide translocase but can be mimicked by chemical uncouplers. Inducible proton conductance is catalyzed by specific uncoupling proteins. We discuss the opportunities and pitfalls of targeting these processes as a treatment for obesity by decreasing coupling efficiency and increasing energy expenditure, either directly or through central mechanisms of energy homeostasis.
Harper
Mary-Ellen
ME
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada K1H 8M5. MaryEllen.Harper@uottawa.ca
Green
Katherine
K
Brand
Martin D
MD
D000255:Adenosine Triphosphate / Q000378:metabolism; D001481:Basal Metabolism / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D015398:Signal Transduction; D014475:Uncoupling Agents / Q000378:metabolism
D014475:Uncoupling Agents; D000255:Adenosine Triphosphate