title: The kinetic basis of threshold effects observed in mitochondrial diseases: a systemic approach.
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.
authors.affiliation: Université Bordeaux II, France.
authors.forename: T
authors.initials: T
authors.lastname: Letellier
authors.forename: R
authors.initials: R
authors.lastname: Heinrich
authors.forename: M
authors.initials: M
authors.lastname: Malgat
authors.forename: J P
authors.initials: JP
authors.lastname: Mazat
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008659:Metabolic Diseases / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000201:enzymology*; D011190:Potassium Cyanide / Q000494:pharmacology; D051381:Rats
chemical_list: D003576:Electron Transport Complex IV; D011190:Potassium Cyanide