Doctorant : E2C
Université Lyon 1
CNRS, UMR 5023 - LEHNA,
Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés
F-69622 Villeurbanne Cedex FRANCE
(+33) 04 72 43 28 99 (33) 04 72 43 11 41
- Body size (M) is a major factor of animal’s life history. It scales with the metabolic rate (MR) according to the following equation: MR = aMb, with b which could vary between ,2-3. as a result of surface-related constraints on fluxes of resources, wastes and heat, and 1 as a result of mass constraints on energy use (Glazier 2008).
Most of studies investigated metabolic rate at the individual scale measuring oxygen consumption of whole-animals and showed a positive relationship with longevity or body size. But, all the consumed oxygen is not use to produce ATP in cells. Moreover, animals produce 90 % of their energy from nutrients by their mitochondria, particularly thanks to their Electron Transfert Chain (ETC) via oxidative phosphorylation (Mitchell 1961). The nutrients undergo different processes, in particular Krebs cycle or β-oxidation, to give reduced coenzymes: NADH and FADH2. These reduced coenzymes yield an electron pair to ETC complexes which will transfer until last complex to serve at oxygen reduction into water molecules. This electron transfer along the ETC leads to a proton expulsion from the mitochondrial matrix to the mitochondrial intermembrane space leading to the production of a proton-motive force (proton gradient) which will be used by the ATP-synthase to generate ATP via ADP phosphorylation. Although, ATP production depends on oxygen oxidation, the number of ATP molecules produced for each oxygen atom consumed can vary (ATP/O ratio)(Porter 2001 ; Brand 2005) due to variation of H+/O ratio which is substrate-dependent, to slippage proton pump or to dissipation of proton gradient across the inner mitochondrial membrane related to the increase of heat production. The degree of coupling between oxidation and ADP phosphorylation to ATP varies across tissues, individuals, environment and species (Salin et al. 2015).
My research thematic consists to study the relationship between the three factors -metabolism, longevity and body size - in endotherms (mainly in mammals and birds), not at the scale of whole-animal but at the cellular level, measuring mitochondrial oxygen consumption and ATP production of two tissues metabolically active: liver and gastrocnemius muscle. These measurements allow to take into account ATP production, and not only the oxygen consumption which is just a proxy of metabolism, and to observe eventual variations concerning ATP/O ratio. Our hypothesis is that the long-lived species, and thus the bigger species, have mitochondria more effective (ATP/O more important) than the short lived (or small) species.
In parallel, the mitochondrial production of reactive oxygen species (ROS) is measured to evaluate the oxidative stress of animals in function to their body size and longevity. ROS are free radicals mainly produced in mitochondria as by-products of the oxidative phosphorylation. At low level, these ROS are essential for many cellular functions, especially for the signaling pathways, but at high level they are deleterious causing damages to different cellular components (proteins, DNA, lipids). Some researchers already studied the ROS production and found a negative relationship between ROS production and longevity / body size (Csiszar et al. 2012) or a positive correlation between ROS production and metabolism. Some of them even come to talk about “Free Radical Theory” or “Mitochondrial Free Radical Theory of Aging” (Harman 1956 and 1972) which consider that aging - the physiological, irreversible, endogenous and natural process leading to decrease individual performance and to increase chance to death - is caused by an accumulation of ROS damages (no avoided by the antioxidant defenses). In our study, we expect the same results but we decide to measure this mitochondrial ROS production to get for each individual its mitochondrial oxygen consumption, ATP production and oxidative stress and realize better comparison between these variables.
To summarize, the aim of my thesis consists to reassess the triptych - metabolism, longevity and body size - measuring mitochondrial ATP and ROS production in parallel of oxygen consumption. The mitochondrion being the mainly organelle involves in energy production and oxygen consumption of animals; it seems to be more interesting to study mitochondrial performances to investigate the links the three variables. Moreover, all these measurements are obtained for each animal that will allow strong inter- and intra- species comparisons.
- Rivera-Ingraham, G.A., Barri, K., Boël, M., Farcy, E., Charles, A.L., Geny, B., Lignot, J.H., 2016 - Osmoregulation and Salinity-Induced Oxidative Stress : Is Oxidative Adaptation Determined by Gill Function ? The Journal of Experimental Biology, 219 (Pt 1) : 80–89.