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Does nitric oxide modulate mitochondrial energy generation and apoptosis?

Abstract

The physiological role of nitric oxide (NO) in the maintenance of vascular tone, in synaptic transmission and in cellular defence is now firmly established. Recent evidence indicates that NO can also affect mitochondrial function. Here, we review findings indicating that NO — through its interaction with components of the electron-transport chain — might function not only as a physiological regulator of cell respiration, but also to augment the generation of reactive oxygen species by mitochondria, and thereby trigger mechanisms of cell survival or death.

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Figure 1: Cytochrome oxidase is an important step in controlling the mitochondrial respiration rate in the presence of nitric oxide.
Figure 2: Generation of reactive oxygen species following inhibition of cytochrome oxidase by nitric oxide.

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Acknowledgements

The authors wish to thank A. Higgs for her valuable contribution to this manuscript. We have drawn from an extensive literature and would like to acknowledge the considerable contributions of those colleagues whom, because of space constraints, we have not been able to quote.

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Correspondence to Salvador Moncada.

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DATABASES

LocusLink:

GAPDH

 Swiss-Prot:

HIF-1α

eNOS

nNOS

iNOS

p21

vascular endothelial growth factor

FURTHER READING

Encyclopedia of Life Sciences:

Mitochondria: structure and role in respiration

Nitric oxide: role in human disease

Nitric oxide: synthesis and action

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Moncada, S., Erusalimsky, J. Does nitric oxide modulate mitochondrial energy generation and apoptosis?. Nat Rev Mol Cell Biol 3, 214–220 (2002). https://doi.org/10.1038/nrm762

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