Mitochondrial Respiratory Chain Adjustment to Cellular Energy Demand

Abstract

Because adaptation to physiological changes in cellular energy demand is a crucial imperative for life, mitochondrial oxidative phosphorylation is tightly controlled by ATP consumption. Nevertheless, the mechanisms permitting such large variations in ATP synthesis capacity, as well as the consequence on the overall efficiency of oxidative phosphorylation, are not known. By investigating several physiological models in vivo in rats (hyper-and hypothyroidism, polyunsaturated fatty acid deficiency, and chronic ethanol intoxication) we found that the increase in hepatocyte respiration (from 9.8 to 22.7 nmol of O 2 /min/mg dry cells) was tightly correlated with total mitochondrial cytochrome content, expressed both per mg dry cells or per mg mitochondrial protein. Moreover, this increase in total cytochrome content was accompanied by an increase in the respective proportion of cytochrome oxidase; while total cytochrome content increased 2-fold (from 0.341 ؎ 0.021 to 0.821 ؎ 0.024 nmol/mg protein), cytochrome oxidase increased 10-fold (from 0.020 ؎ 0.002 to 0.224 ؎ 0.006 nmol/mg protein). This modification was associated with a decrease in the overall efficiency of the respiratory chain. Since cytochrome oxidase is well recognized for slippage between redox reactions and proton pumping, we suggest that this dramatic increase in cytochrome oxidase is responsible for the decrease in the overall efficiency of respiratory chain and, in turn, of ATP synthesis yield, linked to the adaptive increase in oxidative phosphorylation capacity.In aerobic living systems, oxidative phosphorylation activity can vary widely to adequately match ATP synthesis to energy demand according to physiological or pathological conditions. In contrast to short-term adaptation, which relies only on a flux modulation through every functional unit of mitochondrial oxidative phosphorylation, chronic adaptation to various rates of ATP utilization can also be achieved by modifying the number of these functional units (mitogenesis). Indeed, in the light of the large physiological variations in ATP turnover observed in living systems, it is highly probable that the amount of enzymes involved in the oxidative phosphorylation pathway plays a significant role. Recently the trade-off between rate and yield of ATP synthesis in heterotrophic organisms has been highlighted as a possible major mechanism of cooperation and competition involved in the evolutionary aspects of energy metabolism (1).By investigating the effect on the yield of ATP synthesis (ATP/O) 1 after acute modulations of the flux through the oxidative phosphorylation pathway in yeast mitochondria, it has been shown that the decrease in flux was accompanied by an increase in efficiency when the flux was limited by substrate supply (2-4). Conversely, no change in ATP/O was observed when the oxidative phosphorylation flux was modulated by the inhibition of ATP synthesis (oligomycin) (2-4). Hence, depending on the mechanism permitting to modulate the flux through the respiratory chain, different cons...

Effects of Intrusive Force on Selected Determinants of Pulp Vitality

“…Activation of mitogenesis was observed under various conditions to modestly disturb the mitochondrial oxidative phosphorylation system. 34 Severe injury to the pulp cells and their membrane structures seems unlikely in our study because if that were to occur, AST would be released from mitochondria and cells and, accordingly, its activity would be decreased.…”

“…However, the increased enzymatic activity observed in our study might be due to orthodontic force-induced proliferation of pulp cells and activation of mitogenesis. 34 Oxygen is essential for the aerobic production of sources of cellular energy such as adenosine triphosphate (ATP) in mitochondria. One in vitro study of pulp cell responses to hypoxia 35 has suggested that hypoxia might enhance the mitochondrial function and proliferative activity of pulp cells in situ.…”

Determination of mitochondrial reactive oxygen species: methodological aspects

“…Mitochondrion metabolism permits to adequately match ATP synthesis to cellular energy demand according to physiological and/or pathological constraints. This adaptation occurs not only in terms of changing the activity of oxidative phosphorylation pathway, but also in terms of efficiency of this pathway, mitochondrial ATP production being a permanent compromise between rate and efficiency [4].…”

Liver mitochondrial properties from the obesity-resistant Lou/C rat

“…Such effects are reminiscent to those observed with hyperthyroidism. 17 However, we have previously reported that neither triiodithyronine (T3) nor thyroxine (T4) plasma levels were modified in Lou/C rats. 15 The effects of thyroid hormones are, however, dependent on the quantity of the hormone that reaches peripheral tissues and the availability of thyroid receptors in cell nuclei.…”

“…17 J O2 was measured as described above in a medium containing 125 mM KCl, 1 mM EGTA, 5 mM Tris-Pi, 20 mM Tris-HCl, 0.1% fat-free BSA (pH 7.2), and were modulated by addition of increasing concentrations of hexokinase.…”