Mitochondrial nitric oxide synthase regulates mitochondrial matrix pH.
Nitric oxide (nitrogen monoxide, NO) exerts a wide profile of its biological activities via regulation of respiration and respiration-dependent functions. The presence of nitric oxide synthase (NOS) in mitochondria (mtNOS) was recently reported by us (Ghafourifar and Richter, FEBS Lett. 418, 291-296, 1997) and others (Giulivi et al., J. Biol. Chem. 273, 11038-11043, 1998). Here we report that NO, provided by an NO donor as well as by mtNOS stimulation, regulates mitochondrial matrix pH, transmembrane potential and Ca2+ buffering capacity. Exogenously-added NO causes a dose-dependent matrix acidification. Also mtNOS stimulation, induced by loading mitochondria with Ca2+, causes mitochondrial matrix acidification and a drop in mitochondrial transmembrane potential. Inhibition of mtNOS's basal activity causes mitochondrial matrix alkalinization and provides a resistance to the sudden drop of mitochondrial transmembrane potential induced by mitochondrial Ca2+ uptake. We conclude that mtNOS plays a critical role in regulating mitochondrial delta(pH).
Ghafourifar
P
P
Institute of Biochemistry, Swiss Federal Institute of Technology (ETH), Zürich.
Richter
C
C
D002118:Calcium / Q000378:metabolism; D004579:Electron Transport; D006863:Hydrogen-Ion Concentration; D008928:Mitochondria / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*
D019001:Nitric Oxide Synthase; D002118:Calcium