Mitochondrial metabolic states regulate nitric oxide and hydrogen peroxide diffusion to the cytosol

BOVERIS A; VALDEZ LB; ZAOBORNYJ T; BUSTAMANTE J

Moscú, Rusia

Congreso; 14th European Bioenergetics Conference; 2006

Mitochondria isolated from rat heart, liver, kidney and brain (respiratory control 4.0 - 6.5) release NO and H2O2 at rates that depend on the mitochondrial metabolic state: releases are higher in state 4, about 1.7-2.0 times for NO and 4-16 times for H2O2, than in state 3. NO release in rat liver mitochondria showed an exponential dependence on membrane potential in the range 55 to 180 mV, as determined by Rh-123 fluorescence. A similar behavior was reported for mitochondrial H2O2 production by Korshunov et al. (FEBS Lett. 416, 1997, 15-18). Transition from state 4 to state 3 of brain cortex mitochondria was associated to a decrease in NO release (50%) and in membrane potential (24-53%), this latter determined by flow cytometry and DiOC6 and JC-1 fluorescence. The fraction of cytosolic NO provided by diffusion from mitochondria was 61% in heart, 47% in liver, 30% in kidney, and 18% in brain. The data supports the speculation that NO and H2O2 report a high mitochondrial energy charge to the cytosol. Regulation of mtNOS activity by membrane potential makes mtNOS a regulable enzyme that in turn regulates mitochondrial O2 uptake and H2O2 production.