CONICET | Buscador de Institutos y Recursos Humanos

The recognition that NO is a reversible inhibitor of cytochrome oxidase activity competitively with O2 produced a copernican revolution in the understanding of the regulation of respiration, specially at low tissue pO2. It is now understood that tissue O2 uptake depends on the O2/NO ratio, a concept that has both experimental and mathematical support. Mitochondrial O2- production, stimulated by NO itself, removes the NO-inhibition of cytochrome oxidase providing the reversibility of the regulatory mechanism. The calculated intramitochondrial NO levels (100-360 nM) are in the range of the concentrations, 80-200 nM NO, that inhibit by 50 % cytochrome oxidase activity. Mitochondria have their own source of NO with mtNOS, a transcript of nNOS-a, an integral protein of the inner membrane and a voltage-dependent enzyme, whose activity inhibits mitochondrial O2 uptake. Mitochondrial NO has a role in cell signaling: decreased mtNOS activity leads to cell proliferation and increased mtNOS activity leads to cell arrest. Over stimulated mtNOS activity and increased NO mitochondrial levels are associated with mitochondrial dysfunction and nitrative and nitrosative stress in a series of pathophysiological conditions.