IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Bioenergetic regulation of nitric oxide production in rat mitochondria
Autor/es:
VALDEZ LB; ZAOBORNYJ T; BOMBICINO SS; BOVERIS A
Lugar:
Dublin, Irlanda
Reunión:
Congreso; 15th European Bioenergetics Conference; 2008
Institución organizadora:
European Bioenergetics Society
Resumen:
Not only heart mitochondrial membranes (2.08±0.08 nmol/min.mg protein), but also heart coupled
mitochondria, exhibit an enzymatic production of NO.
MtNOS activity is 40% lower in
state 3 than in state 4, and shows an exponential dependence on membrane
potential. The aim of this work was to further characterize mtNOS activity
regulation by the redox state of the respiratory chain and membrane potential. The
generation of NO (nmol/min.mg protein) by heart submitochondrial particles
resulted 0.45±0.02. This value was enhanced up to 0.81±0.09 when mtNOS activity was assessed in the
presence of succinate and ATP. The addition of rotenone inhibited by 50% this
reversed electron transfer-supported mtNOS activity. Besides, the ability of mtNOS to modulate O2 uptake
and H2O2 production, is termed mtNOS functional activity. Supplementation of state 3 mitochondria with
L-arginine decreased respiration rates by 15-20%, while addition of L-NAME
increased O2 consumption by 10%. The
addition of L-arginine enhanced state 4 H2O2 production
by 14-21%, whereas supplementation with L-NAME declined H2O2
generation by 7-9%. Interestingly, these effects were observed in coupled mitochondria,
but not in mitochondrial membranes. We conclude through direct and indirect
evidence, that mtNOS activity is regulated by membrane potential; and that
respiratory chain electron flow modulates NO production; in agreement with the
reported physical interaction of mtNOS and respiratory chain components.