Mitochondrial complex I inactivation after ischemia-reperfusion in the stunned heart

BOMBICINO SS; D'ANNUNZIO V; VALDEZ LB; RUKAVINA MIKUSIC IA; IGLESIAS DE

Advances in Biochemistry in Health and Disease. Biochemistry of oxidative stress: Physiopathology and clinical aspects

Springer

Lugar: New York; Año: 2016; p. 245 - 257

Mitochondrial complex I (NADH-ubiquinone oxidoreductase) catalyzes the transfer of two electrons from NADH via flavin mononucleotide (FMN) and a series of iron-sulfur centers (Fe-S) to ubiquinone (UQ), in a reaction associated with proton translocation across the inner membrane, contributing to the proton-motive force. Complex I produces superoxide anion (O2-) through the auto-oxidation reaction of flavin-semiquinone (FMNH?) with molecular oxygen. Superoxide reacts with nitric oxide (NO) to yield peroxynitrite (ONOO-), a strong oxidant and nitrating compound. When the steady-state concentration of ONOO- is enhanced, tyrosine nitration, protein oxidation and damage to Fe-S centers might takes place, leading to a sustained complex I inhibition. Dysfunction of complex I was found in a number of clinical conditions such as Parkinson?s disease, ischemia-reperfusion, endotoxic shock, and aging. We have shown that the ventricular dysfunction observed in myocardial stunning is associated with a mitochondrial dysfunction that includes partial inactivation of complex I and mitochondrial nitric oxide synthase (mtNOS) activities, oxidative and/or nitrosative damage and increased hydrogen peroxide (H2O2) and ONOO- production rates. Moreover, adenosine proved to be effective in attenuating ventricular dysfunction and also in protecting from mitochondrial dysfunction and complex I syndrome.