EVIDENCE THAT THE BLOCKADE OF MITOCHONDRIAL RESPIRATION BY THE NEUROTOXIN 1-METHYL-4-PHENYLPYRIDINIUM (MPP+) INVOLVES BINDING AT THE SAME SITE AS THE RESPIRATORY INHIBITOR, ROTENONE

被引:70
作者
KRUEGER, MJ
SINGER, TP
CASIDA, JE
RAMSAY, RR
机构
[1] VET ADM MED CTR,DIV MOLEC BIOL,SAN FRANCISCO,CA 94121
[2] UNIV CALIF SAN FRANCISCO,DIV TOXICOL,SAN FRANCISCO,CA 94143
[3] UNIV CALIF BERKELEY,DEPT ENTOMOL,BERKELEY,CA 94720
关键词
D O I
10.1016/0006-291X(90)91442-U
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
It has been postulated that 1-methyl-4-phenylpyridinium (MPP+) blocks mitochondrial respiration by combining at the same site as rotenone, a potent inhibitor of NADH oxidation in mitochondria, known to act at the junction of NADH dehydrogenase and coenzyme Q (CoQ). The present experiments show that MPP+ and two of its analogs indeed act in a concentration dependent manner to prevent the binding of [14C]-rotenone to submitochondrial particles (ETP) and significantly decrease the inhibition of electron transport caused by rotenone. It therefore appears that MPP+ binds at the same site as rotenone or an adjacent site, supporting the hypothesis that its neurotoxic action is due to the inhibition of mitochondrial respiration. © 1990.
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收藏
页码:123 / 128
页数:6
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