Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease Article

Carreras, MC, Franco, MC, Peralta, JG et al. (2004). Nitric oxide, complex I, and the modulation of mitochondrial reactive species in biology and disease . Molecular Aspects of Medicine, 25(1-2), 125-139. 10.1016/j.mam.2004.02.014

cited authors

  • Carreras, MC; Franco, MC; Peralta, JG; Poderoso, JJ

authors

abstract

  • Mitochondria are the specialized organelles for energy metabolism but also participate in the production of O2 active species, cell cycle regulation, apoptosis and thermogenesis. Classically, regulation of mitochondrial energy functions was based on the ADP/ATP ratio, which dynamically stimulates the transition between resting and maximal O2 uptake. However, in the last years, NO was identified as a physiologic regulator of electron transfer and ATP synthesis by inhibiting cytochrome oxidase. Additionally, NO stimulates the mitochondrial production of O 2 active species, primarily O2- and H 2O2, and, depending on NO matrix concentration, of ONOO-, which is responsible for the nitrosylation and nitration of mitochondrial components. By this means, alteration in mitochondrial complexes restricts energy output, further increases O2 active species and changes cell signaling for proliferation and apoptosis through redox effects on specific pathways. These mechanisms are prototypically operating in prevalent generalized diseases like sepsis with multiorgan failure or limited neurodegenerative disorders like Parkinson's disease. Complex I appears to be highly susceptible to ONOO- effects and nitration, which defines an acquired group of mitochondrial disorders, in addition to the genetically induced syndromes. Increase of mitochondrial NO may follow over-expression of nNOS, induction and translocation of iNOS, and activation and/or increased content of the newly described mtNOS. Likewise, mtNOS is important in the modulation of O2 uptake and cell signaling, and in mitochondrial pathology, including the effects of aging, dystrophin deficiency, hypoxia, inflammation and cancer. © 2004 Elsevier Ltd. All rights reserved.

publication date

  • February 1, 2004

published in

Digital Object Identifier (DOI)

start page

  • 125

end page

  • 139

volume

  • 25

issue

  • 1-2