METABOLIC CONTROL ANALYSIS AND THRESHOLD EFFECT IN OXIDATIVE-PHOSPHORYLATION - IMPLICATIONS FOR MITOCHONDRIAL PATHOLOGIES

We have shown that the Metabolic Control Analysis (MCA) can explain th e threshold effect observed in the expression of mitochondrial disease s [8]. As a matter of fact, the effect of a specific inhibitor on the flux of O-2 consumption mimics a defect in a step of oxidative phospho rylation. The observed threshold is correlated to the value of the con trol coefficient of the inhibited step. For this reason, we have studi ed the repartition of the control coefficients of different steps in o xidative phosphorylation on various tissues (liver, kidney, brain, ske letal muscle and heart). We discuss the results in terms of metabolic control theory and provide a possible explanation for the heterogeneou s phenotype of those pathologies. We present the double threshold hypo thesis of both a threshold in the energy demand of a tissue and in the energy supply by oxidative phosphorylation.