IBIMOL   23987
INSTITUTO DE BIOQUIMICA Y MEDICINA MOLECULAR PROFESOR ALBERTO BOVERIS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Complex I functionally interacts with mitochondrial nitric oxide synthase (mtNOS)
Autor/es:
BOMBICINO S; IGLESIAS DE; ZAOBORNYJ T; BOVERIS A; VALDEZ LB
Lugar:
Sierra de la Ventana
Reunión:
Congreso; XLIII Reunión Anual de la Sociedad Argentina de Biofísica; 2014
Institución organizadora:
Sociedad Argentina de Biofísica
Resumen:
The functional association between complex I and mitochondrial nitric oxide synthase (mtNOS) was studied. Bovine heart phosphorylating electron transfer particles (ETPH-Mg2+) showed a NAD+ reductase activity of 13.6 ± 0.7 nmol/min.mg protein, sustained by reversed electron flow of the respiratory chain, at expenses of ATP when succinate was added. This activity was inhibited by rotenone (88%), oligomycin (98%) and m-CCCP (93%). ETPH-Mg2+ produced NO at a rate of 0.79 ± 0.06 nmol NO/min.mg protein by the classic NOS reaction. In the presence of 0.5 mM MgCl2 and 0.3 mM KCN and of the compounds needed to carry out the reverse electron flow, ETPH-Mg2+ produced 0.46 ± 0.03 nmol NO/min.mg protein by electron transfer from complex I to mtNOS. Rotenone inhibited (80%) mtNOS activity supported by reversed electron flow, but that inhibitor did not reduce the activity of isolated nNOS, indicating that the inhibitory effect of rotenone on NO production by ETPH-Mg2+ is due to an electron flow blockage and not to a direct action on mtNOS structure. A heart mitochondrial fraction enriched in complex I was recognized by anti-nNOS antibodies. Altogether, the data obtained in ETPH-Mg2+ suggest that complex I interacts physically and functionally with mtNOS. Electrons from reversed electron flow or from complex I reductants support NO production, in agreement with the dependences of mtNOS activity on mitochondrial metabolic state and on membrane potential.