Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension

Nitric oxide (nitrogen monoxide, NO) at low concentrations can potently deenergize isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. Deenergization is observed when mitochondria utilize respiratory substrates such as pyruvate plus malate, succinate, or ascorbate plus tetramethylphenylenediamine, but not when mitochondria are energized with ATP. The extent and duration of deenergization is determined by the concentration of NO and oxygen, and the kind of respiratory substrate. The NO-induced changes of the mitochondrial energy state are transient and are paralleled by release and reuptake of mitochondrial calcium. These findings reveal a direct action of NO on the mitochondrial respiratory chain and suggest that NO exerts some of its physiological and pathological effects by deenergizing mitochondria.