Abstract
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 autoxidation reaction of the 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 take 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 nitrosative damages and increased 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.
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Acknowledgment
This work was supported by grants from the University of Buenos Aires (UBACYT 20020110100140, 20020130100731 and 20020130100557), Agencia Nacional de Promoción Científica y Tecnológica (PICT 2013-0373, 2014-0964), and Consejo Nacional de Investigaciones Científicas y Técnicas (PIP 11220110100444).
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Valdez, L.B., Bombicino, S.S., Iglesias, D.E., Rukavina-Mikusic, I.A., D’Annunzio, V. (2016). Mitochondrial Complex I Inactivation After Ischemia-Reperfusion in the Stunned Heart. In: Gelpi, R., Boveris, A., Poderoso, J. (eds) Biochemistry of Oxidative Stress. Advances in Biochemistry in Health and Disease, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-319-45865-6_16
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DOI: https://doi.org/10.1007/978-3-319-45865-6_16
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