Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes

J. Stadler*, T. R. Billiar, R. D. Curran, D. J. Stuehr, J. B. Ochoa, R. L. Simmons

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Although nitric oxide (·N = O) biosynthesis is inducible in rat hepatocytes (HC), the physiological significance of ·N = O production by these cells is unknown. Short exposure of HC to authentic ·N = O led to a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubiquinone oxidoreductase (complexes I and II of the mitochondrial electron transport chain). Most susceptible to ·N = O inhibition was mitochondrial aconitase, in which a reduction in enzyme activity to 20.2 ± 1.6% of control was observed. In contrast to mitochondrial aconitase, cytosolic aconitase activity was not inhibited by ·N = O. After exposure to a maximal inhibitory concentration of ·N = O, mitochondrial aconitase activity recovered completely within 6 h. Complex I did not fully recover within this incubation period. Endogenous ·N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide. After 18 h of incubation with these stimuli, a significant inhibition of mitochondrial aconitase activity to 70.8 ± 2.4% of controls was detected. However, this was due only in part to the action of ·N = O. A non-·N = O-dependent inhibition of mitochondrial function appeared to be mediated by tumor necrosis factor.

Original languageEnglish
Pages (from-to)C910-C916
JournalAmerican Journal of Physiology - Cell Physiology
Issue number5 29-5
StatePublished - 1991


  • 4Fe-4S cluster
  • Aconitase
  • Reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase
  • Succinate-ubiquinone oxidoreductase
  • Tumor necrosis factor-α


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