title: Rotenone-mediated changes in intracellular coenzyme A thioester levels: implications for mitochondrial dysfunction.
abstract: Rotenone, an organic pesticide and potent mitochondrial complex I inhibitor, causes Parkinson-like neurodegeneration in rodents and is implicated in human Parkinson's disease. In this rapid report, rotenone induced a dose-dependent decrease in succinyl-coenzyme A (CoA) and increase in β-hydroxybutyryl-CoA in multiple human cell lines (IC(50) < 100 nM). Rotenone also inhibited [U-(13)C(6)]-glucose-derived [(13)C]-acetyl-CoA and [(13)C]-succinyl-CoA biosynthesis in SH-SY5Y neuroblastoma cells. These changes are compatible with a compensatory metabolic rearrangement. Stable isotope dilution liquid chromatography-mass spectrometry and CoA thioester isotopomer analysis provided insight into mechanisms of rotenone toxicity, which will facilitate the development of new biomarkers of mitochondrial dysfunction.
authors.affiliation: Centers for Cancer Pharmacology and Excellence in Environmental Toxicology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104-6160, United States.
authors.forename: Sankha S
authors.initials: SS
authors.lastname: Basu
authors.forename: Ian A
authors.initials: IA
authors.lastname: Blair
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism*; D045744:Cell Line, Tumor; D002853:Chromatography, Liquid / Q000379:methods; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007306:Insecticides / Q000494:pharmacology*; D013058:Mass Spectrometry / Q000379:methods; D010205:Pantothenic Acid / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology*
chemical_list: D000214:Acyl Coenzyme A; D007306:Insecticides; D012402:Rotenone; D010205:Pantothenic Acid; C030372:3-hydroxybutyryl-coenzyme A; C012046:succinyl-coenzyme A; D005947:Glucose