Mitochondrial oxygen radical formation during reductive and oxidative stress to intact hepatocytes.

Abstract

After simple respiratory inhibition, glycolytic substrates prevent cell death by providing an alternate source of cellular ATP. When mitochondrial uncoupling ensues, the uncoupler-stimulated mitochondrial ATPase hydrolyzes ATP formed by glycolysis and protection is lost. Electron transfer components abnormally reduced by respiratory inhibition, especially ubisemiquinone, react directly with oxygen to form toxic radicals. Mitochondria also generate reactive oxygen species after exposure to oxidant chemicals. A consequence is onset of the mitochondrial permeability transition, which leads to uncoupling, cellular ATP depletion and loss of viability. Thus, mitochondria are both a source and a target of toxic oxygen radicals in cell injury.