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Am J Physiol Endocrinol Metab 291: E460-E467, 2006. First published April 18, 2006; doi:10.1152/ajpendo.00258.2005
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Influence of intensity of food restriction on skeletal muscle mitochondrial energy metabolism in rats

Gyasi Johnson, Damien Roussel, Jean-François Dumas, Olivier Douay, Yves Malthièry, Gilles Simard, and Patrick Ritz

Institut National de la Santé et de la Recherche Médicale, Unité 694; Université d'Angers; and Laboratoire de biochimie et biologie moléculaire, Centre Hospitalier Universitaire Angers, Angers, France

Submitted 9 June 2005 ; accepted in final form 24 March 2006

Variable durations of food restriction (FR; lasting weeks to years) and variable FR intensities are applied to animals in life span-prolonging studies. A reduction in mitochondrial proton leak is suggested as a putative mechanism linking such diet interventions and aging retardation. Early mechanisms of mitochondrial metabolic adaptation induced by FR remain unclear. We investigated the influence of different degrees of FR over 3 days on mitochondrial proton leak and mitochondrial energy metabolism in rat hindlimb skeletal muscle. Animals underwent 25, 50, and 75% and total FR compared with control rats. Proton leak kinetics and mitochondrial functions were investigated in two mitochondrial subpopulations, intermyofibrillar (IMF) and subsarcolemmal (SSM) mitochondria. Regardless of the degree of restriction, skeletal muscle mass was not affected by 3 days of FR. Mitochondrial basal proton conductance was significantly decreased in 50% restricted rats in both mitochondrial subpopulations (46 and 40% for IMF and SSM, respectively) but was unaffected in other groups compared with controls. State 3 and uncoupled state 3 respiration rates were decreased in SSM mitochondria only for 50% restricted rats when pyruvate + malate was used as substrate (–34.5 and –38.9% compared with controls, P < 0.05). IMF mitochondria respiratory rates remained unchanged. Three days of FR, particularly at 50% FR, were sufficient to lower mitochondria energetic metabolism in both mitochondrial populations. Our study highlights an early step in mitochondrial adaptation to FR and the influence of the severity of restriction on this adaptation. This step may be involved in an aging-retardation process.

proton leak; oxidative phosphorylation; mitochondria



Address for reprint requests and other correspondence: P. Ritz, 4 rue Larrey, Medecine B, CHU, F-49033 Angers Cedex 01, France (e-mail: paritz{at}chu-angers.fr)







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