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
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
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DOI：
10.1016/0006-291x(90)91442-u
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发表时间：
1990-05-31
影响因子：
3.1
通讯作者：
RAMSAY, RR
中科院分区：
文献类型：
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作者：
KRUEGER, MJ;SINGER, TP;RAMSAY, RR
据推测，1-甲基-4-苯基吡啶鎓 (MPP+) 通过与鱼藤酮在同一位点结合来阻断线粒体呼吸，鱼藤酮是线粒体中 NADH 氧化的有效抑制剂，已知在 NADH 脱氢酶和辅酶 Q (CoQ) 的连接处发挥作用。目前的实验表明，MPP+及其两种类似物确实以浓度依赖的方式起作用，以防止[14C]-鱼藤酮与下软骨颗粒（ETP）结合，并显着降低由鱼藤酮引起的电子传递的抑制。因此，MPP+ 似乎与鱼藤酮结合在同一位点或相邻位点，支持了其神经毒性作用是由于抑制线粒体呼吸而产生的假设。
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.