Inhibition of mitochondrial NADH-ubiquinone oxidoreductase activity and ATP synthesis by tetrahydroisoquinoline.
Effects of tetrahydroisoquinoline (TIQ) on mitochondrial respiration, NADH-ubiquinone oxidoreductase (complex I) activity and on adenosine triphosphate (ATP) synthesis were studied using mitochondria prepared from mouse brains. Tetrahydroisoquinoline significantly inhibited mitochondrial respiration supported by glutamate + malate, pyruvate + malate or alpha-ketoglutarate. Activity of complex I and synthesis of ATP were also significantly inhibited by TIQ. Mitochondrial respiration supported by succinate and subsequent ATP synthesis were not inhibited at all by 5 mM of TIQ. Our study has revealed a novel action of TIQ, which has been proposed as a candidate for an endogenous substance that may induce Parkinson's disease.
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000201:enzymology*; D016660:NAD(P)H Dehydrogenase (Quinone); D010101:Oxygen Consumption / Q000187:drug effects*; D011808:Quinone Reductases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D000255:Adenosine Triphosphate; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases