Phylogenetic differences of mammalian basal metabolic rate are not explained by mitochondrial basal proton leak

Abstract

Metabolic rates of mammals presumably increased during the evolution of endothermy, but molecular and cellular mechanisms underlying basal metabolic rate (BMR) are still not understood. It has been established that mitochondrial basal proton leak contributes significantly to BMR. Comparative studies among a diversity of eutherian mammals showed that BMR correlates with body mass and proton leak. Here, we studied BMR and mitochondrial basal proton leak in liver of various marsupial species. Surprisingly, we found that the mitochondrial proton leak was greater in marsupials than in eutherians, although marsupials have lower BMRs. To verify our finding, we kept similar-sized individuals of a marsupial opossum (Monodelphis domestica) and a eutherian rodent (Mesocricetus auratus) species under identical conditions, and directly compared BMR and basal proton leak. We confirmed an approximately 40 per cent lower mass specific BMR in the opossum although its proton leak was significantly higher (approx. 60%). We demonstrate that the increase in BMR during eutherian evolution is not based on a general increase in the mitochondrial proton leak, although there is a similar allometric relationship of proton leak and BMR within mammalian groups. The difference in proton leak between endothermic groups may assist in elucidating distinct metabolic and habitat requirements that have evolved during mammalian divergence.

Oxidative phosphorylation efficiency, proton conductance and reactive oxygen species production of liver mitochondria correlates with body mass in frogs

“…This is due to a decrease in the mitochondrial proton conductance in the heaviest individuals. Interestingly, the negative relationship found between mitochondrial proton leak and M b in frogs is similar to that in endothermic groups such as mammals (Porter and Brand, 1993), including marsupials (Polymeropoulos et al, 2012), and birds . Finally, and in contrast to our prediction, we found that liver mitochondria from the larger individuals produced significantly lower levels of ROS than those from the smaller animals.…”

“…However, such interspecific correlation between mammalian M b and mitochondrial ROS generation is not systematically found, being mostly revealed when isolated mitochondria oxidize succinate in the absence of rotenone (Lambert et al, 2007) or when cells are metabolically stressed (Csiszar et al, 2012). However, it is apparent that the negative relationship reported between M b and proton leak (Porter and Brand, 1993;Porter et al, 1996;Polymeropoulos et al, 2012) cannot be associated with a positive allometric variation in ROS generation (Sohal et al, 1989(Sohal et al, , 1990Ku et al, 1993;Lambert et al, 2007;Csiszar et al, 2012). A similar result has been found in birds, with M b shown to be negatively correlated with both proton leak and ROS generation in liver mitochondria respiring on succinate (Lambert et al, 2007;Montgomery et al, 2012).…”

“…The differences in results between studies may simply reflect the disparate nature of the ectotherm species used in each study (fishes, toads, lizards, crocodiles, snails) in addition to the temperature and tissue studied (kidney, liver, skeletal muscle). Although the data were collected from a small number of frog species, they suggest that the negative relationship between proton conductance and M b that is seen in endotherms (Porter and Brand, 1993;Porter et al, 1996;Polymeropoulos et al, 2012) may also occur in frogs. However, this may not necessarily be the case for all groups of ectotherms (Hulbert et al, 2002), as suggested in reptiles, where proton conductance of liver mitochondria from crocodiles appears greater than that of smaller reptiles (Brookes et al, 1998;Hulbert et al, 2002).…”

“…Allometric relationships of proton leak and oxidative activity with animal body size have been observed in the liver mitochondria of endotherms Porter and Brand, 1993;Porter et al, 1996;Polymeropoulos et al, 2012). Proton leak refers to the mechanism where motive force is dissipated through the mitochondrial inner membrane proton conductance pathways independently of ATP synthase.…”

Rediscovering and Reviving Old Observations and Explanations of Metabolic Scaling in Living Systems

“…Recent investigators have implicated membrane composition and function [89,167,179,234], mitochondrial activity and number [97,179,[235][236][237], intracellular transport costs [130], DNA content [182,190], and other biochemical factors [238], as importantly involved in the intrinsic cellular control of metabolic scaling. Evidence for and against various specific aspects of this approach can be found in [19,20,89,[91][92][93][94]130,167,169,[235][236][237][238][239][240][241][242][243]. A major limitation of the cell-based RD approach is that it cannot explain by itself why the hypometric scaling of cellular metabolic rate is lost in cells cultured in vivo (reviewed in [20,97]).…”