RESEARCH ARTICLE David and Goliath: A Mitochondrial Coupling Problem? KARINE SALIN 1∗ , DAMIEN ROUSSEL 1 , BENJAMIN REY 2 , AND YANN VOITURON 1 1 Laboratoire d’Ecologie des Hydrosyst` emes Naturels et Anthropis´ es (U.M.R. CNRS 5023), Universit´ e Claude Bernard Lyon 1, Universit´ e de Lyon, Villeurbanne, France 2 Laboratoire de Biom´ etrie et Biologie Evolutive (U.M.R. CNRS 5558), Universit´ e Claude Bernard Lyon 1, Universit´ e de Lyon, Villeurbanne, France An organism’s size, known to affect biological structures and processes from cellular metabolism to population dynamics, depends upon the duration and rate of growth. However, it is still poorly understood how mitochondrial function affects the energetic basis of growth, especially in ec- totherms, which represent a huge majority of animal biodiversity. Here, we present an intraspecies comparison of neighboring populations of frogs (Rana temporaria) that have large differences in body mass even at the same age. By investigating liver mitochondrial bioenergetics, we find that frogs with high growth rates and large body sizes exhibit higher ATP synthesis rates and more efficient oxidative phosphorylation compared to the smaller frogs with low growth rates. This higher energy transduction efficiency is not associated with significant increased oxidative capac- ity or membrane potential values, but instead may rely on a higher mitochondrial phosphorylation system activity in combination with a lower inner membrane proton leakage. Overall, the present study introduces the mitochondrial energy transduction system as an important mechanism for balancing physiological and ecological trade-offs associated with body size. Whether phenotype differences in mitochondrial function result from local ecological constraints or reflect a natural genetic variability within wild populations of common frogs remains an open question. However, our findings highlight the need for closer consideration of all aspects of mitochondrial metabolism for a better understanding of the physiological basis of the link between size, metabolism, and energy production in wild-dwelling organisms. J. Exp. Zool. 317:283–293, 2012. © 2012 Wiley Periodicals, Inc. How to cite this article: Salin K, Roussel D, Rey B, Voituron Y. 2012. David and Goliath: A mitochondrial coupling problem? J. Exp. Zool. 317:283–293. ABSTRACT J. Exp. Zool. 317:283–293, 2012 As William A. Calder (’84) stated, “there is no doubt that body size is a major factor in an animal’s life history and require- ments.” Indeed, an organism’s size, which can range nearly 2000-fold in vertebrates from the gecko Sphaeradactylus ari- asae (16 mm long) to the blue whale Balaenoptera musculus (30 m long), affects the state of all of its biological structures and processes, from cellular metabolism up to population dy- namics (Peters and Wassenberg, ’83; Banavar et al., 2010). As all biological activities depend on energy, a considerable ef- fort for over 150 years has been put forth to document the relation between body size and energy metabolism. Respira- tory metabolic rate (R) typically scales with body mass (M) according to the power function R = αM b , where α is a nor- malization constant, and b is the scaling exponent, which is usually 0.75, though this is still under much debate (West et al., 2003; Banavar et al., 2010). Because of its link with energy metabolism, body size has a strong impact on whole body per- formances, such as tolerance to environmental variations such as temperature and food deprivation, and on physical capacities, such as running speed and diving performance (Schreer and Ko- vacs, ’97). At the subcellular level, studies performed mainly in Grant Sponsor: French Ministry of Research and Education. ∗ Correspondence to: Karine Salin, Ecology of Natural and Man-impacted Hydrosystems (U.M.R. CNRS 5023), Universit´ e Claude Bernard Lyon 1, 43 Bvd 11 Novembre 1918, 69622 Villeurbanne Cedex, France. E-mail: karine.salin@univ-lyon1.fr Received 22 August 2011; Revised 1 February 2012; Accepted 2 February 2012 Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jez.1722 © 2012 WILEY PERIODICALS, INC.