Oxygen-Dependent Reversible Inhibition of Mitochondrial Respiration by Nitric Oxide

Cell Structure and Function

Yoko Inai²  Alan A. Horton¹  Keisuke Hamazaki²  Kozo Utsumi²  Yoshiki Takehara²  Munehisa Yabuki²  Tamotsu Yoshioka²  Masayasu Inoue³  Hiroko Nakahara² 

[1] School of Biochemistry, University of Birmingham;Institute of Medical Science, Center for Adult Diseases;Department of Biochemistry, Osaka City University Medical School

关键词: nitric oxide;    mitochondria;    respiration;    oxygen tension;    energy metabolism;    NOC 18;    SIN-1;   

DOI  :  10.1247/csf.21.251

学科分类：分子生物学，细胞生物学和基因

来源: Japan Society for Cell Biology

【 摘 要 】

References(47)Cited-By(18)Effects of nitric oxide (NO) and NO generating agents, on the electron transport system of mitochondria were examined in a study of the mechanism and physiological importance of NO in energy metabolism. In the presence of various substrates, uncoupled respiration was inhibited by NO in manner which was both dose- and oxygen tension-dependent. Simultaneously measuring changes in cytochrome absorption spectra and respiration showed that the site of action of NO is cytochrome oxidase. Similar inhibition was also brought about by 1-hydroxy-2-oxo-3, 3-bis(2-aminoethyl)-1-triazene (NOC 18), an NO donor. Electron paramagnetic resonance (EPR) analysis revealed that inhibition of uncoupled respiration occurred only during the presence of NO in the reaction mixture. The inhibitory effect of NO was increased significantly by lowering the concentration of mitochondrial protein. No appreciable inhibition of respiration was observed in the presence of 3-morpholinosydnonimine (SIN-1), a peroxynitrite anion (ONOO-) generating reagent, but inhibition did occur in the presence of superoxide dismutase (SOD). These results indicate that NO reversibly interacts with mitochondria at complex IV thereby inhibiting respiration particularly under physiologically low oxygen tension and that de novo generated ONOO- may have no significant effect under the present experimental conditions.

【 授权许可】

Unknown