Activation of Hsp90/NOS and increased NO generation does not impair mitochondrial respiratory chain by competitive binding at cytochrome C Oxidase in low oxygen concentrations

Tennille Presley, Kaushik Vedam, Xiaoping Liu, Jay L. Zweier, Govindasamy Ilangovan

Research output: Contribution to journalArticlepeer-review

Abstract

Nitric oxide (NO) is known to regulate mitochondrial respiration, especially during metabolic stress and disease, by nitrosation of the mitochondrial electron transport chain (ETC) complexes (irreversible) and by a competitive binding at O2 binding site of cytochrome c oxidase (CcO) in complex IV (reversible). In this study, by using bovine aortic endothelial cells, we demonstrate that the inhibitory effect of endogenously generated NO by nitric oxide synthase (NOS) activation, by either NOS stimulators or association with heat shock protein 90 (Hsp90), is significant only at high prevailing p02 through nitrosation of mitochondrial ETC complexes, but it does not inhibit the respiration, by competitive binding at CcO at very low p02. ETC complexes activity measurements confirmed that significant reduction in complex IV activity was noticed at higher p0 2, but it was unaffected at low pO2 in these cells. This was further extended to heat-shocked cells, where NOS was activated by the induction/activation of (Hsp90) through heat shock at an elevated temperature of 420C. From these results, we conclude that the entire attenuation of respiration by endogenous NO is due to irreversible inhibition by nitrosation of ETC complexes but not through reversible inhibition by competing with O 2 binding at CcO at complex IV.

Original languageEnglish (US)
Pages (from-to)611-627
Number of pages17
JournalCell Stress and Chaperones
Volume14
Issue number6
DOIs
StatePublished - Nov 2009
Externally publishedYes

Keywords

  • Electron transport chain
  • Heat shock proteins
  • Nitric oxide synthases
  • Oxygen metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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