title: Metabolomic profiling rationalized pyruvate efficacy in cybrid cells harboring MELAS mitochondrial DNA mutations.
abstract: Pyruvate treatment was found to alleviate clinical symptoms of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome and is highly promising therapeutic. Using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS), we measured time-changes of 161 intracellular and 85 medium metabolites to elucidate metabolic effects of pyruvate treatment on cybrid human 143B osteosarcoma cells harboring normal (2SA) and MELAS mutant (2SD) mitochondria. The results demonstrated dramatic and sustainable effects of pyruvate administration on the energy metabolism of 2SD cells, corroborating pyruvate as a metabolically rational treatment regimen for improving symptoms associated with MELAS and possibly other mitochondrial diseases.
authors.affiliation: Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0017, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kami
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.forename: Saori
authors.initials: S
authors.lastname: Igarashi
authors.forename: Sayaka
authors.initials: S
authors.lastname: Koike
authors.forename: Shoko
authors.initials: S
authors.lastname: Sugawara
authors.forename: Satsuki
authors.initials: S
authors.lastname: Ikeda
authors.forename: Naomi
authors.initials: N
authors.lastname: Sato
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.forename: Masaru
authors.initials: M
authors.lastname: Tomita
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Soga
mesh_terms: D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics; D019075:Electrophoresis, Capillary; D004734:Energy Metabolism; D006801:Humans; D017241:MELAS Syndrome / Q000503:physiopathology*; D055442:Metabolome; D009154:Mutation; D019289:Pyruvic Acid / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D004272:DNA, Mitochondrial; D019289:Pyruvic Acid