Abstract
In the present study we show the existence of a functional nitric oxide synthase (NOS) in rat liver mitochondria. The enzyme uses l-arginine ( l-arg) to produce nitric oxide (NO) and l-citrulline, and is Ca 2+-dependent. l-Arg analogues, N ω-monomethyl- l-arg and N ω-nitro- l-arg, inhibit the enzyme, and d-arginine is not a substrate for it. We found mitochondrial NOS (mtNOS) activity associated with the inner mitochondrial membrane but not with the matrix fraction. In intact, succinate-energized mitochondria, the enzyme is constitutively active and exerts substantial control over mitochondrial respiration and membrane potential. The activity is further stimulated when Ca 2+ is taken up by mitochondria. We suggest that the existence of mtNOS and its Ca 2+ dependence are highly relevant for mitochondrial functioning.
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