NO and H2O2 difusion from mitochondria.

VALDEZ LB; ZAOBORNYJ T; BOVERIS A

Aguas de Lindoia, San Pablo, Brasil.

Congreso; IV Meeting of the South American Group of the Society for Free Radical Biology and Medicine; 2005

South American Group of the Society for Free Radical Biology and Medicine

Nitric oxide (NO) production by the co-oxidation of L-arginine and NADPH by O2 has been observed in mitochondrial membranes isolated from a series of mammalian organs. The responsible enzyme has been named mitochondrial nitric oxide synthase (mtNOS). Nitric oxide diffusion from mitochondria is markedly higher in state 4 than in state 3. The rates of NO release by liver, kidney and heart mitochondria were about 40-50% lower in state 3 (0.7, 0.4, and 0.4 nmol/min.mg prot.) than in state 4 (1.3, 0.7, and 0.6 nmol/min.mg prot.). The decrease in NO release in the state 4-state 3 transition is opposite to what could be expected from the matrix acidification of the state 4-state 3 transition and the pH dependence of mtNOS activity. The changes in NO production by mitochondrial nitric oxide synthase (mtNOS) are driven by membrane potential. In the same way, ion movements through the inner mitochondrial membrane modify the rates of hydrogen peroxide (H2O2) production, which supports the concept that membrane potential regulates ubisemiquinone auto-oxidation. A high mitochondrial protonic potential is linked to high productions of NO and superoxide anion (O2-), this latter the stoichiometric precursor of H2O2. The data seems to support the hypothesis that NO and H2O2 may constitute a diffusible signal to report a high mitochondrial energy charge to the cell.