Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease

Free Radic Biol Med. 2010 Aug 1;49(3):307-16. doi: 10.1016/j.freeradbiomed.2010.04.004. Epub 2010 Apr 11.


The effects of nitric oxide in biological systems depend on its steady-state concentration and where it is being produced. The organ where nitric oxide is produced is relevant, and within the organ, which types of cells are actually contributing to this production seem to play a major determinant of its effect. Subcellular compartmentalization of specific nitric oxide synthase enzymes has been shown to play a major role in health and disease. Pathophysiological conditions affect the cellular expression and localization of nitric oxide synthases, which in turn alter organ cross talk. In this study, we describe the compartmentalization of nitric oxide in organs, cells, and subcellular organelles and how its localization relates to several relevant clinical conditions. Understanding the complexity of the compartmentalization of nitric oxide production and the implications of this compartmentalization in terms of cellular targets and downstream effects will eventually contribute toward the development of better strategies for treating or preventing pathological events associated with the increase, inhibition, or mislocalization of nitric oxide production.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Asthma / physiopathology
  • Cell Compartmentation
  • Enzyme Activation
  • Gene Expression Regulation, Enzymologic
  • Half-Life
  • Humans
  • Isoenzymes / metabolism
  • Liver / enzymology
  • Liver Diseases / physiopathology
  • Lung / enzymology
  • Muscle, Skeletal / enzymology
  • Muscular Diseases / physiopathology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Pneumonia / physiopathology
  • Protein Transport / physiology
  • Signal Transduction / drug effects
  • Subcellular Fractions / enzymology*


  • Isoenzymes
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III