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


: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.


Free Radic Res


Free radical research


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




Has Abstract


2018-12-01 00:00:00












  • A(1) and A(3) adenosine receptors alter glutathione status in an organ-specific manner and influence the changes after inhibition of gamma-glutamylcysteine ligase.

    abstract::Adenosine levels are increased in stress and act as anti-oxidant and anti-inflammatory mediators by binding to 4 G-protein-coupled receptors. Using genetically modified mice lacking A(1) and A(3) adenosine receptors, treated with ip buthionine-[S,R]-sulphoximine injections to inhibit gamma-glutamylcysteine ligase, the...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Conte C,Grottelli S,Prudenzi E,Bellezza I,Fredholm BB,Minelli A

    更新日期:2009-03-01 00:00:00

  • Oxidative inactivation of the proteasome in Alzheimer's disease.

    abstract::In the present study we isolated proteasome complexes from control, mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects. No significant difference in the amount of proteasomes was detected across the different groups, although impairments in chymotrypsin-like proteasome activity was observed in AD s...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Cecarini V,Ding Q,Keller JN

    更新日期:2007-06-01 00:00:00

  • Synthesis and spin trapping properties of polystyrene supported trifluoromethylated cyclic nitrones.

    abstract::Polystyrene supported fluorinated cyclic nitrone spin-traps: Resin-2-HFDMPO (2-hydroxymethyl-2-methyl-5-(trifluoromethyl)-3,4-dihydro-2H-pyrrole-1-oxide) and Resin-2-PFDMPO (2-(3-hydroxypropyl)-2-methyl-5-(trifluoromethyl)-3,4-dihydro-2H-pyrrole 1-oxide) containing a trifluoromethyl pyrroline-N-oxide core were develop...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Earla A,Walter ED,Braslau R

    更新日期:2019-12-01 00:00:00

  • Chronic antioxidant therapy reduces oxidative stress in a mouse model of Alzheimer's disease.

    abstract::Oxidative modifications are a hallmark of oxidative imbalance in the brains of individuals with Alzheimer's, Parkinson's and prion diseases and their respective animal models. While the causes of oxidative stress are relatively well-documented, the effects of chronically reducing oxidative stress on cognition, patholo...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Siedlak SL,Casadesus G,Webber KM,Pappolla MA,Atwood CS,Smith MA,Perry G

    更新日期:2009-02-01 00:00:00

  • SOD2 gene polymorphism and response of oxidative stress parameters in young wrestlers to a three-month training.

    abstract::The aim of the study was to analyse the effect of Val 16Ala polymorphism in SOD2 gene on oxidative stress parameters and lipid profile of the blood during a three-month wrestling training. The study included 53 Polish young wrestlers. Blood samples were collected at the beginning of the programme and following three m...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Jówko E,Gierczuk D,Cieśliński I,Kotowska J

    更新日期:2017-05-01 00:00:00

  • Aldehyde adducts generated during lipid peroxidation modification of proteins.

    abstract::Various lines of evidence indicate that an important part in the pathogenesis of atherosclerosis is the modification of the plasma low-density lipoproteins (LDLs). A large number of pro-inflammatory and pro-atherogenic properties have been ascribed to the oxidatively modified LDLs and their components. There is consid...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Uchida K

    更新日期:2015-01-01 00:00:00

  • Coenzyme Q10 depletion is comparatively less detrimental to human cultured skin fibroblasts than respiratory chain complex deficiencies.

    abstract::The oxidative stress possibly resulting from an inherited respiratory chain (RC) deficiency was investigated in a series of human cultured skin fibroblasts presenting either ubiquinone depletion or isolated defect of the various RC complexes. Taken as an index for superoxide overproduction, a significant induction of ...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Geromel V,Rötig A,Munnich A,Rustin P

    更新日期:2002-04-01 00:00:00

  • Hydroxyl radical scavenging activity of nonsteroidal anti-inflammatory drugs.

    abstract::The hydroxyl radical (.OH)-scavenging activity of d-2-[4-(3-methyl-2-thienyl)phenyl]propionic acid (M-5011), a novel nonsteroidal anti-inflammatory drug (NSAID), and that of several other NSAIDs were investigated by the hyaluronic acid (HA) degradation method and the electron spin resonance (ESR) spin-trapping techniq...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Kataoka M,Tonooka K,Ando T,Imai K,Aimoto T

    更新日期:1997-10-01 00:00:00

  • Melatonin nitrosation promoted by NO*2; comparison with the peroxynitrite reaction.

    abstract::N-nitroso species have recently been detected in animal tissues. Protein N-nitrosotryptophan is the best candidate for this N-nitroso pool. N-nitrosation of N-blocked trytophan derivatives like melatonin (MelH) by N2O3 or peroxynitrite (ONOOH/ONOO- ) has been observed under conditions of pH and reagent concentrations ...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Peyrot F,Houée-Levin C,Ducrocq C

    更新日期:2006-09-01 00:00:00

  • Redox properties of the nitronyl nitroxide antioxidants studied via their reactions with nitroxyl and ferrocyanide.

    abstract::Nitronyl nitroxides (NNs) are the paramagnetic probes that are capable of scavenging physiologically relevant reactive oxygen (ROS) and nitrogen (RNS) species, namely superoxide, nitric oxide (NO), and nitroxyl (HNO). NNs are increasingly considered as potent antioxidants and potential therapeutic agents. Understandin...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Bobko AA,Khramtsov VV

    更新日期:2015-01-01 00:00:00

  • Sequential molecular changes and dynamic oxidative stress in high-grade serous ovarian carcinogenesis.

    abstract::The mechanism of high-grade serous ovarian cancer (HGSC) development remains elusive. This review outlines recent advances in the understanding of sequential molecular changes associated with the development of HGSC, as well as describes oxidative stress-induced genomic instability and carcinogenesis. This article rev...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Kobayashi H,Ogawa K,Kawahara N,Iwai K,Niiro E,Morioka S,Yamada Y

    更新日期:2017-10-01 00:00:00

  • Severe total hepatic ischemia and reperfusion: relationship between very high alpha-tocopherol uptake and lipid peroxidation.

    abstract::Reperfusion injury of the liver occurs in liver transplantation and in major hepatectomies. It triggers a severe oxidative stress that leads to increased lipid peroxidation. In our study we examined the effect of parenteral supranutritional administration of alpha-tocopherol, a vitamin that plays a key role in the end...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Giakoustidis D,Kontos N,Iliadis S,Papageorgiou G,Tsantilas D,Spyridis C,Papazoglou K,Botsoglou N,Dimitriadou A,Giakoustidis E

    更新日期:2001-08-01 00:00:00

  • Electrophilic oxysterols: generation, measurement and protein modification.

    abstract::Cholesterol is an essential component of mammalian plasma membrane. Alterations in sterol metabolism or oxidation have been linked to various pathological conditions, including cardiovascular diseases, cancer, and neurodegenerative disorders. Unsaturated sterols are vulnerable to oxidation induced by singlet oxygen an...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Miyamoto S,Lima RS,Inague A,Viviani LG

    更新日期:2021-01-26 00:00:00

  • Hydrazyl-nitrones, novel hybrid molecules in free radical research.

    abstract::This work describes the synthesis and characterisation of some novel hybrid molecules which contains in the same molecule a free radical moiety of hydrazyl type and a spin-trap moiety of nitrone type. The new compounds synthesized have multiple and easy to follow spectroscopic properties, making them useful as sensors...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Ionita P

    更新日期:2006-01-01 00:00:00

  • Analysis of dichlorodihydrofluorescein and dihydrocalcein as probes for the detection of intracellular reactive oxygen species.

    abstract::Dihydrocalcein (H2-calcein) is recommended as a superior probe for intracellular radical (ROS) detection as different to dichlorodihydrofluorescein (H2-DCF), its oxidation product calcein is thought not to leak out of cells. We determined whether H2-calcein is a useful tool to measure ROS in vascular smooth muscle cel...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Keller A,Mohamed A,Dröse S,Brandt U,Fleming I,Brandes RP

    更新日期:2004-12-01 00:00:00

  • Methods of quantitative analysis of the nitric oxide metabolites nitrite and nitrate in human biological fluids.

    abstract::In human organism, the gaseous radical molecule nitric oxide (NO) is produced in various cells from L-arginine by the catalytic action of NO synthases (NOS). The metabolic fate of NO includes oxidation to nitrate by oxyhaemoglobin in red blood cells and autoxidation in haemoglobin-free media to nitrite. Nitrate and ni...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Tsikas D

    更新日期:2005-08-01 00:00:00

  • Red-wine beneficial long-term effect on lipids but not on antioxidant characteristics in plasma in a study comparing three types of wine--description of two O-methylated derivatives of gallic acid in humans.

    abstract::The purpose of this double clinical study was (1) to evaluate the effect of one single intake (300 ml) of red wine (RW) on the plasma antioxidant capacity (pAOC) and plasma phenolics over the 24-h time period following the intake, and (2) to compare the long-term effects of daily intakes (250 ml/d) of RW, white wine (...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Cartron E,Fouret G,Carbonneau MA,Lauret C,Michel F,Monnier L,Descomps B,Léger CL

    更新日期:2003-09-01 00:00:00

  • Prophylactic role of taurine on arsenic mediated oxidative renal dysfunction via MAPKs/ NF-kappaB and mitochondria dependent pathways.

    abstract::The present study has been designed and carried out to investigate the protective role of taurine (2-aminoethanesulphonic acid) against NaAsO(2) induced nephrotoxicity. Oral administration of arsenic increased the productions of ROS and RNS, enhanced lipid peroxidation, protein carbonylation and decreased intracellula...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Roy A,Manna P,Sil PC

    更新日期:2009-10-01 00:00:00

  • Quantum mechanical and experimental oxidation studies of pentadecylresorcinol, olivetol, orcinol and resorcinol.

    abstract::Resorcinols (pentadecylresorcinol, olivetol, orcinol and resorcinol) exhibit antioxidant properties in liposomal systems. Antioxidant potency depends on the length of the alkyl chain. Pentadecylresorcinol has been demonstrated to be the most active antioxidant, indicating significance of its alkyl chain in a lipid bil...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Hładyszowski J,Zubik L,Kozubek A

    更新日期:1998-04-01 00:00:00

  • Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl-hydroxychroman (gamma-CEHC).

    abstract::Cigarette smoking is associated with increased oxidative stress and increased risk of degenerative disease. As the major lipophilic antioxidant, requirements for vitamin E may be higher in smokers due to increased utilisation. In this observational study we have compared vitamin E status in smokers and non-smokers usi...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Jeanes YM,Hall WL,Proteggente AR,Lodge JK

    更新日期:2004-08-01 00:00:00

  • Salicylate trapping of .OH as a tool for studying post-ischemic oxidative injury in the isolated rat heart.

    abstract::The use of salicylate as a chemical trap for .OH represents a simple and convenient alternative to the use of spin trapping techniques to study oxidative injury in isolated perfused organs. In these systems, salicylate is included in the perfusion buffer at concentrations ranging from 0.1 to 2 mM depending on the dete...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Powell SR

    更新日期:1994-11-01 00:00:00

  • Malondialdehyde and 4-hydroxy-2-nonenal in plant tissue cultures: LC-MS determination of 2,4-dinitrophenylhydrazone derivatives.

    abstract::The cytologically active secondary lipid peroxidation products, malondialdehyde (MDA) and 4-hydroxy-2-nonenal (HNE) have been detected as their 2,4-dinitrophenylhydrazone (DNP) derivatives in plant tissue cultures using LC-MS. This paper reports, for the first time, the use of LC-MS methodology to definitively identif...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Deighton N,Magill WJ,Bremner DH,Benson EE

    更新日期:1997-09-01 00:00:00

  • A novel method using 8-hydroperoxy-2'-deoxyguanosine formation for evaluating antioxidative potency.

    abstract::Degenerative diseases such as cancer are induced by oxidative genetic damage. Antioxidants can scavenge reactive oxygen species, but to prevent disease, they must do so quickly, before the DNA bases are damaged. In the present study, a novel method was established for evaluating the potency of antioxidants employing 2...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Sakakibara H,Ashida H,Kanazawa K

    更新日期:2002-03-01 00:00:00

  • Cyp4a14 overexpression induced by hyperoxia in female CBA mice as a possible contributor of increased resistance to oxidative stress.

    abstract::The beneficial effects of hyperoxia have been noted in treatment of several diseases and pathological states. However, the excessive production of ROS under hyperoxic conditions can directly damage cellular macromolecules if the imbalance in antioxidant status exists. Cytochrome P450 (Cyp) 4a14 has an important role i...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Sobocanec S,Balog T,Sarić A,Sverko V,Zarković N,Gasparović AC,Zarković K,Waeg G,Macak-Safranko Z,Kusić B,Marotti T

    更新日期:2010-02-01 00:00:00

  • Posttranslational protein modifications by reactive nitrogen and chlorine species and strategies for their prevention and elimination.

    abstract::Proteins are subject to various posttranslational modifications, some of them being undesired from the point of view of metabolic efficiency. Prevention of such modifications is expected to provide new means of therapy of diseases and decelerate the process of aging. In this review, modifications of proteins by reacti...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Sadowska-Bartosz I,Ott C,Grune T,Bartosz G

    更新日期:2014-11-01 00:00:00

  • DNA strand scission by the nephrotoxin [2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide and related compounds in the presence of iron.

    abstract::The capacity of non-illuminated nephrotoxin orellanine ([2,2'-bipyridine]-3,3',4,4'-tetrol-1,1'-dioxide) to induce DNA damage in the presence of ferrous iron and dioxygen has been evaluated. Maximal single-strand breaks in plasmid DNA were obtained with a metal to ligand ratio 1:3. Instantaneous oxidation of Fe2+ in p...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Cantin-Esnault D,Oubrahim H,Richard JM

    更新日期:2000-08-01 00:00:00

  • The effect of myoglobin on the stability of the hydroxyl-radical adducts of 5,5 dimethyl-1-pyrolline-N-oxide (DMPO), 3,3,5,5 tetramethyl-1-pyrolline-N-oxide (TMPO) and 1-alpha-phenyl-tert-butyl nitrone (PBN) in the presence of hydrogen peroxide.

    abstract::The hydroxyl radical adducts of 5,5 dimethyl-1-pyrolline-N-oxide (DMPO) and 3,3,5,5 tetramethyl-1-pyrolline-N-oxide (TMPO) formed in the presence of hydrogen peroxide and FeII are normally quite stable, but in the presence of 5-20 micromolar myoglobin their ESR signals decay rapidly. This decay probably reflects furth...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: De Bono D,Yang WD,Symons MC

    更新日期:1994-05-01 00:00:00

  • Haem oxygenase-1 inhibits neointimal hyperplasia in rat by histone deacetylase 2.

    abstract::It has been reported that haem oxygenase-1 (Hmox1) induction attenuates neointimal thickening. Here we further investigated the potential mechanisms regulating this important pathological process. We revealed that histone deacetylase 2 (HDAC2) was induced following Hmox1 induction under 1% oxygen treatment and this in...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Ni J,Yang W,Shen W,Zhang R

    更新日期:2018-10-01 00:00:00

  • Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

    abstract::Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and...

    journal_title:Free radical research

    pub_type: 杂志文章


    authors: Kaikkonen JE,Kresanov P,Ahotupa M,Jula A,Mikkilä V,Viikari JS,Juonala M,Hutri-Kähönen N,Kähönen M,Lehtimäki T,Kangas AJ,Soininen P,Ala-Korpela M,Raitakari OT

    更新日期:2016-01-01 00:00:00

  • Sjøgren's syndrome-associated oxidative stress and mitochondrial dysfunction: prospects for chemoprevention trials.

    abstract::An involvement of oxidative stress (OS) was found in recent studies of Sjøgren's syndrome (SS) that reported significant changes in protein oxidation, myeloperoxidase activity, TNF-α, nitrotyrosine, and GSH levels in plasma from SS patients. Excess levels of OS markers, as oxidative DNA damage and propanoyl-lysine, we...

    journal_title:Free radical research

    pub_type: 杂志文章,评审


    authors: Pagano G,Castello G,Pallardó FV

    更新日期:2013-02-01 00:00:00