Mitochondrial ATP synthase--a possible target protein in the regulation of energy metabolism in vitro and in vivo
2002 (English)In: Nutritional neuroscience, ISSN 1028-415X, Vol. 5, no 3, 201-210 p.Article in journal (Refereed) Published
The increasing prevalence of obesity in the Western world has stimulated an intense search for mechanisms regulating food intake and energy balance. A number of appetite-regulating peptides have been identified, their receptors cloned and the intracellular events characterized. One possible energy-dissipating mechanism is the mitochondrial uncoupling of ATP-synthesis from respiratory chain oxidation through uncoupling proteins, whereby energy derived from food could be dissipated as heat, instead of stored as ATP. The exact role of the uncoupling proteins in energy balance is, however, uncertain. We show here that mitochondrial F1F0-ATP synthase itself is a target protein for an anorectic peptide, enterostatin, demonstrated both after affinity purification of rat brain membranes and through a direct physical interaction between enterostatin and purified F1-ATP synthase. In insulinoma cells (INS-1) enterostatin was found to target F1F0-ATP synthase, causing an inhibition of ATP production, an increased thermogenesis and increased oxygen consumption. The experiments suggest a role of mitochondrial F1F0-ATP synthase in the suppressed insulin secretion induced by enterostatin. It could be speculated that this targeting mechanism is involved in the decreased energy efficiency following enterostatin treatment in rat.
Place, publisher, year, edition, pages
2002. Vol. 5, no 3, 201-210 p.
Animals, Calorimetry, Cattle, Colipases/pharmacology, Cross-Linking Reagents, Energy Metabolism, Insulin/secretion, Insulinoma/metabolism, Male, Mitochondria/*enzymology, Oxygen Consumption, Pancreatic Neoplasms/metabolism, Protein Precursors/pharmacology, Proton-Translocating ATPases/*metabolism, Rats, Rats; Sprague-Dawley, Tumor Cells; Cultured
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-10413DOI: 10.1080/10284150290008604PubMedID: 12041876OAI: oai:DiVA.org:uu-10413DiVA: diva2:38181