Coenzyme Q10 serves to couple mitochondrial oxidative phosphorylation and fatty acid β-oxidation, and attenuates NLRP3 inflammasome activation

Suphannee Chokchaiwong, Yung Ting Kuo, Shih Hsiang Lin, Yi Ching Hsu, Sung Po Hsu, Yu Ting Liu, An Je Chou, Shu Huei Kao

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Multiple acyl-CoA dehydrogenase deficiency (MADD), an autosomal recessive metabolic disorder of fatty acid metabolism, is mostly caused by mutations in the ETFA, ETFB or ETFDH genes that result in dysfunctions in electron transfer flavoprotein (ETF) or electron transfer flavoprotein-ubiquinone dehydrogenase (ETFDH). In β-oxidation, fatty acids are processed to generate acyl-CoA, which is oxidised by flavin adenine dinucleotide and transfers an electron to ETF and, through ETFDH, to mitochondrial respiratory complex III to trigger ATP synthesis. Coenzyme Q10 (CoQ10) is believed to be a potential treatment that produces symptom relief in some MADD patients. CoQ10 acts as a key regulator linking ETFDH and mitochondrial respiratory complex III. Our aim is to investigate the effectiveness of CoQ10 in serving in the ETF/ETFDH system to improve mitochondrial function and to reduce lipotoxicity. In this study, we used lymphoblastoid cells with an ETFDH mutation from MADD patients. ETFDH dysfunction caused insufficient β-oxidation, leading to increasing lipid droplet and lipid peroxide accumulation. In contrast, supplementation with CoQ10 significantly recovered mitochondrial function and concurrently decreased the generation of reactive oxygen species and lipid peroxides, inhibited the accumulation of lipid droplets and the formation of the NOD-like receptor family pyrin domain-containing three (NLRP3) inflammasome, and reduced interleukin-1β release and cell death. These results clarify the causal role of CoQ10 in coupling the electron transport chain with β-oxidation, which may promote the development of CoQ10-directed therapies for MADD patients.

Original languageEnglish
Pages (from-to)1445-1455
Number of pages11
JournalFree Radical Research
Issue number11-12
Publication statusPublished - Dec 2 2018


  • Coenzyme Q10
  • electron transfer flavoprotein dehydrogenase
  • inflammasome
  • mitochondrial function
  • multiple acyl-CoA dehydrogenase deficiency

ASJC Scopus subject areas

  • Biochemistry


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