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Mitochondria and Nitric Oxide: Chemistry and Pathophysiology

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Advances in Mitochondrial Medicine

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 942))

Abstract

Cell respiration is controlled by nitric oxide (NO) reacting with respiratory chain complexes, particularly with Complex I and IV. The functional implication of these reactions is different owing to involvement of different mechanisms. Inhibition of complex IV is rapid (milliseconds) and reversible, and occurs at nanomolar NO concentrations, whereas inhibition of complex I occurs after a prolonged exposure to higher NO concentrations. The inhibition of Complex I involves the reversible S-nitrosation of a key cysteine residue on the ND3 subunit. The reaction of NO with cytochrome c oxidase (CcOX) directly involves the active site of the enzyme: two mechanisms have been described leading to formation of either a relatively stable nitrosyl-derivative (CcOX-NO) or a more labile nitrite-derivative (CcOX-NO −2 ). Both adducts are inhibited, though with different KI; one mechanism prevails on the other depending on the turnover conditions and availability of substrates, cytochrome c and O2. SH-SY5Y neuroblastoma cells or lymphoid cells, cultured under standard O2 tension, proved to follow the mechanism leading to degradation of NO to nitrite. Formation of CcOX-NO occurred upon rising the electron flux level at this site, artificially or in the presence of higher amounts of endogenous reduced cytochrome c. Taken together, the observations suggest that the expression level of mitochondrial cytochrome c may be crucial to determine the respiratory chain NO inhibition pathway prevailing in vivo under nitrosative stress conditions. The putative patho-physiological relevance of the interaction between NO and the respiratory complexes is addressed.

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Abbreviations

CcOX:

cytochrome c oxidase

I/R:

ischemia and reperfusion

Mb:

myoglobin

NO:

nitric oxide

NOS:

nitric oxide synthase

ONOO− :

peroxynitrite

OXPHOS:

oxidative phosphorylation

ROS:

reactive oxygen species

SNO-MPG:

S-nitroso-2-mercaptopropionyl-glicine.

TMPD:

tetramethyl-p-phenylendiamine

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Acknowledgments

Work partially supported by Ministero dell’Istruzione, dell’Università e della Ricerca of Italy to P.S. (PRIN “Metabolismo Energetico dell’Ossigeno e del Monossido di Azoto: Fisiologia e Patologia”).

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Authors and Affiliations

  1. Department of Biochemical Sciences ‘A. Rossi Fanelli’, University of Rome “La Sapienza”, Piazzale Aldo Moro 5, I-00185, Rome, Italy

    Paolo Sarti, Marzia Arese, Elena Forte & Daniela Mastronicola

  2. CNR Institute of Molecular Biology and Pathology, University of Rome “La Sapienza”, I-00185, Rome, Italy

    Alessandro Giuffrè

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  1. Paolo Sarti
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  2. Marzia Arese
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  3. Elena Forte
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Correspondence to Paolo Sarti .

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  1. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Roberto Scatena

  2. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Patrizia Bottoni

  3. School of Medicine, Institute of Biochemistry and Clinical B, Catholic University, Largo A. Gemelli 8, Rome, 00168, Italy

    Bruno Giardina

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Sarti, P., Arese, M., Forte, E., Giuffrè, A., Mastronicola, D. (2012). Mitochondria and Nitric Oxide: Chemistry and Pathophysiology. In: Scatena, R., Bottoni, P., Giardina, B. (eds) Advances in Mitochondrial Medicine. Advances in Experimental Medicine and Biology, vol 942. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2869-1_4

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