MITOCHONDRIAL OXYGEN RADICAL FORMATION DURING REDUCTIVE AND OXIDATIVESTRESS TO INTACT HEPATOCYTES

After simple respiratory inhibition, glycolytic substrates prevent cel l death by providing an alternate source of cellular ATP, When mitocho ndrial uncoupling ensues, the uncoupler-stimulated mitochondrial ATPas e hydrolyzes ATP formed by glycolysis and protection is lost. Electron transfer components abnormally reduced by respiratory inhibition, esp ecially ubisemiquinone, react directly with oxygen to form toxic radic als. Mitochondria also generate reactive oxygen species after exposure to oxidant chemicals. A consequence is onset of the mitochondrial per meability transition, which leads to uncoupling, cellular ATP depletio n and loss of viability. Thus, mitochondria are both a source and a ta rget of toxic oxygen radicals in cell injury.