The kinetic basis of threshold effects observed in mitochondrial diseases: a systemic approach
T Letellier1, R Heinrich, M Malgat
1Université Bordeaux II, France.
Abstract:
Threshold effects in the expression of metabolic diseases have often been observed in mitochondrial pathologies, i.e. the clinical demonstration of the disease appears only when the activity of a step has been reduced to a rather low level. We show experimentally that an inhibition of cytochrome c oxidase activity by cyanide, simulating a defect in this step, leads to a decrease in mitochondrial respiration which then exhibits a threshold behaviour similar to that observed in mitochondrial diseases. We discuss this behaviour in terms of metabolic control theory and construct a mathematical model simulating this behaviour.
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