Nitric oxide synthase activity in mitochondria.
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 Ca2+-dependent. L-Arg analogues, N(omega)monomethyl-L-arg and N(omega)-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 Ca2+ is taken up by mitochondria. We suggest that the existence of mtNOS and its Ca2+ dependence are highly relevant for mitochondrial functioning.
Ghafourifar
P
P
Laboratory of Biochemistry I, Swiss Federal Institute of Tehchnology, (ETH), Zurich, Switzerland.
Richter
C
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats
D019001:Nitric Oxide Synthase; D002118:Calcium