Aspects, mechanism, and biological relevance of mitochondrial protein nitration sustained by mitochondrial nitric oxide synthase

S. L. Elfering, V. L. Haynes, Nathaniel Traaseth, A. Ettl, Cecilia Giulivi

Research output: Contribution to journalArticle

Abstract

The goal of this study was to explore the occurrence of nitrated proteins in mitochondria given that these organelles are endowed with a mitochondrial nitric oxide (NO·) synthase and considering the important role that mitochondria have in energy metabolism. Our hypothesis is that nitration of proteins constitutes a posttranslational modification by which NO· exhibits long-term effects above and beyond those bioregulatory ones mediated through the interaction with cytochrome c oxidase. Our studies are aimed at understanding the mechanisms underlying the nitration of proteins in mitochondria and the biological significance of such a process in the cellular milieu. On promoting a sustained NO· production by mitochondria, we investigated various aspects of protein nitration. Among them, the localization of nitrated proteins in mitochondrial subfractions, the identification of nitrated proteins through proteomic approaches, the characterization of affected pathways, and depiction of a target sequence. The biological relevance was analyzed by considering the turnover of native and nitrated proteins. In this regard, mitochondrial dysfunction, ensuing nitrative stress, may be envisioned as the result of accumulation of nitrated proteins, resulting from an overproduction of endogenous NO· (this study), a failure in the proteolytic system to catabolize modified proteins, or a combination of both. Finally, this study allows one to gain understanding on the mechanism and nitrating species underlying mitochondrial protein nitration.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number1 55-1
StatePublished - Jan 2004

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Mitochondrial Proteins
Nitric Oxide Synthase
Mitochondria
Proteins
Nitric Oxide
Electron Transport Complex IV
Post Translational Protein Processing
Organelles
Proteomics
Energy Metabolism

Keywords

  • Aging
  • Mitochondria
  • Nitrotyrosine
  • Oxidative stress
  • Proteomics

ASJC Scopus subject areas

  • Physiology

Cite this

Aspects, mechanism, and biological relevance of mitochondrial protein nitration sustained by mitochondrial nitric oxide synthase. / Elfering, S. L.; Haynes, V. L.; Traaseth, Nathaniel; Ettl, A.; Giulivi, Cecilia.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 1 55-1, 01.2004.

Research output: Contribution to journalArticle

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AU - Giulivi, Cecilia

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