title: β-Lapachone attenuates mitochondrial dysfunction in MELAS cybrid cells.
abstract: Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is a mitochondrial disease caused by mutations in the mitochondrial genome. This study investigated the efficacy of β-lapachone (β-lap), a natural quinone compound, in rescuing mitochondrial dysfunction in MELAS cybrid cells. β-Lap significantly restored energy production and mitochondrial membrane potential as well as normalized the elevated ROS level in MELAS cybrid cells. Additionally, β-lap reduced lactic acidosis and restored glucose uptake in the MELAS cybrid cells. Finally, β-lap activated Sirt1 by increasing the intracellular NAD(+)/NADH ratio, which was accompanied by increased mtDNA content. Two other quinone compounds (idebenone and CoQ10) that have rescued mitochondrial dysfunction in previous studies of MELAS cybrid cells had a minimal effect in the current study. Taken together, these results demonstrated that β-lap may provide a novel therapeutic modality for the treatment of MELAS.
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Jeong
authors.affiliation: R&D Center, KT&G Life Sciences Corp., Suwon, Republic of Korea.
authors.forename: Jin Hwan
authors.initials: JH
authors.lastname: Kim
authors.affiliation: R&D Center, KT&G Life Sciences Corp., Suwon, Republic of Korea.
authors.forename: Kang-Sik
authors.initials: KS
authors.lastname: Seo
authors.affiliation: R&D Center, KT&G Life Sciences Corp., Suwon, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kwak
authors.affiliation: College of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea. Electronic address: woojinpark@me.com.
authors.forename: Woo Jin
authors.initials: WJ
authors.lastname: Park
mesh_terms: D004272:DNA, Mitochondrial / Q000235:genetics; D004734:Energy Metabolism / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D017241:MELAS Syndrome / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D009243:NAD; D019344:Lactic Acid; C014638:beta-lapachone
keywords: MELAS; Mitochondria; NQO1; β-Lapachone