Effect of MI-D, a new mesoionic compound, on energy-linked functions of rat liver mitochondria.
MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylami ne chloride), a new mesoionic compound, depressed the phosphorylation efficiency of liver mitochondria as deduced from an accentuated decrease of the respiratory control coefficient and ADP/O ratio. Analysis of segments of the respiratory chain suggested that the MI-D inhibition site is further on than complex I and between complexes II and III. The transmembrane electrical potential (delta psi) was collapsed dependent on MI-D concentration. ATPase activity was dramatically increased by MI-D in intact mitochondria, but inhibited in carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled mitochondria. These results suggest that MI-D acts as an uncoupler agent, a property closely related to its structural characteristics.
Cadena
S M
SM
Departamento de Bioquímica, Universidade Federal do Paraná, Curitiba, Brazil.
Carnieri
E G
EG
Echevarria
A
A
de Oliveira
M B
MB
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects*; D002934:Cinnamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000378:metabolism; D013830:Thiadiazoles; D013844:Thiazoles / Q000494:pharmacology*; D014475:Uncoupling Agents / Q000494:pharmacology*
C116348:4-phenyl-5-(4-nitrocinnamoyl)-1,3,4-thiadiazolium-2-phenylamine; D002934:Cinnamates; D013830:Thiadiazoles; D013844:Thiazoles; D014475:Uncoupling Agents; D018698:Glutamic Acid; D000244:Adenosine Diphosphate; D019802:Succinic Acid; D010088:Oxidoreductases; D000251:Adenosine Triphosphatases; D010100:Oxygen