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

Abstract:

: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.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Chokchaiwong S,Kuo YT,Lin SH,Hsu YC,Hsu SP,Liu YT,Chou AJ,Kao SH

doi

10.1080/10715762.2018.1500695

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

1445-1455

issue

11-12

eissn

1071-5762

issn

1029-2470

journal_volume

52

pub_type

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