THE KINETIC BASIS OF THRESHOLD EFFECTS OBSERVED IN MITOCHONDRIAL DISEASES - A SYSTEMIC APPROACH

Threshold effects in the expression of metabolic diseases have often b een observed in mitochondrial pathologies i.e. the clinical demonstrat ion of the disease appears only when the activity of a step has been r educed to a rather low level. We show experimentally that an inhibitio n 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 mitochondr ial diseases. We discuss this behaviour in terms of metabolic control theory and construct a mathematical model simulating this behaviour.