Mitochondrial ATP synthase--a possible target protein in the regulation of energy metabolism in vitro and in vivo

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine (hsv//eng)

Nyckelord

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

Ins-1

Enterostatin

Insulin

Thermogenesis

Uncoupling Protein

Publikations- och innehållstyp

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