Menadione partially restores NADH-oxidation and ATP-synthesis in complex I deficient fibroblasts.
In this paper we report our studies on the effects of menadione in cultured fibroblasts treated with rotenone to block complex I. A normalization of the lactate to pyruvate ratio after incubation with glucose, an increased production of 14CO2 from [6-14C]glucose and an increased intra-cellular concentration of ATP was observed in the presence of micromolar concentrations of menadione. These results not only demonstrate the potential value of menadione in complex I deficient patients but also suggest that this system can be used advantageously for the in vitro assessment of therapeutic agents for disorders of the mitochondrial respiratory chain.
Wijburg
F A
FA
Department of Pediatrics, University Hospital of Amsterdam (AMC), The Netherlands.
Feller
N
N
de Groot
C J
CJ
Wanders
R J
RJ
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D009243:NAD / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone); D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D011808:Quinone Reductases / Q000037:antagonists & inhibitors*; D012402:Rotenone / Q000494:pharmacology; D014812:Vitamin K / Q000494:pharmacology*
D007773:Lactates; D011773:Pyruvates; D012402:Rotenone; D009243:NAD; D014812:Vitamin K; D019344:Lactic Acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D005947:Glucose