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Mitochondrial Complex I Inactivation After Ischemia-Reperfusion in the Stunned Heart

  • Laura B. ValdezEmail author
  • Silvina S. Bombicino
  • Darío E. Iglesias
  • Ivana A. Rukavina-Mikusic
  • Verónica D’Annunzio
Chapter
Part of the Advances in Biochemistry in Health and Disease book series (ABHD, volume 16)

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.

Keywords

Stunned heart Complex I Mitochondrial nitric oxide synthase (mtNOS) Hydrogen peroxide Nitric oxide Superoxide anion Peroxynitrite 

Notes

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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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Laura B. Valdez
    • 1
    Email author
  • Silvina S. Bombicino
    • 1
  • Darío E. Iglesias
    • 1
  • Ivana A. Rukavina-Mikusic
    • 1
  • Verónica D’Annunzio
    • 2
  1. 1.Institute of Biochemistry and Molecular Medicine (IBIMOL; UBA-CONICET), Physical Chemistry Division, School of Pharmacy and BiochemistryUniversity of Buenos AiresBuenos AiresArgentina
  2. 2.Institute of Biochemistry and Molecular Medicine (IBIMOL; UBA-CONICET), Pathology Division, School of MedicineUniversity of Buenos AiresBuenos AiresArgentina

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