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[PMID]:28084602
[Au] Autor:Zeng J; Deng S; Wang Y
[Ad] Endereço:School of Life Science, Hunan University of Science and Technology, Xiangtan, Hunan, 411201, People's Republic of China. zengj@hnu.edu.cn.
[Ti] Título:Identification of the Catalytic Residue of Rat Acyl-CoA Dehydrogenase 9 by Site-Directed Mutagenesis.
[So] Source:Appl Biochem Biotechnol;182(3):1198-1207, 2017 Jul.
[Is] ISSN:1559-0291
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acyl-CoA dehydrogenase 9 (ACAD 9) is the ninth member of ACADs involved in mitochondrial fatty acid oxidation and possibly complex I assembly. Sequence alignment suggested that Glu389 of rat ACAD 9 was highly conserved and located near the active center and might act as an important base for the dehydrogenation reaction. The role of Glu389 in the catalytic reaction was investigated by site-directed mutagenesis. Both wild-type and mutant ACAD 9 proteins were purified and their catalytic characterization was studied. When Glu389 was replaced by other residues, the enzyme activity could be lost to a large extent. Those results suggested that Glu389 could function as the catalytic base that abstracted the α-proton of the acyl-CoA substrate in a proposed catalytic mechanism.
[Mh] Termos MeSH primário: Acil-CoA Desidrogenases/química
Modelos Químicos
Mutagênese Sítio-Dirigida
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Acil-CoA Desidrogenases/genética
Substituição de Aminoácidos
Animais
Catálise
Domínio Catalítico
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.1.8 (acyl-CoA dehydrogenase (NADP+))
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170626
[Lr] Data última revisão:
170626
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170114
[St] Status:MEDLINE
[do] DOI:10.1007/s12010-016-2392-1


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[PMID]:27438479
[Au] Autor:Fragaki K; Chaussenot A; Boutron A; Bannwarth S; Cochaud C; Richelme C; Sacconi S; Paquis-Flucklinger V
[Ad] Endereço:Nice Sophia Antipolis University, Institute for Research on Cancer and Aging (IRCAN), CNRS, INSERM, UMR 7284 and U1081, School of Medicine, 28 avenue de Valombrose, 06107, Nice cedex 2, France.
[Ti] Título:Severe defect in mitochondrial complex I assembly with mitochondrial DNA deletions in ACAD9-deficient mild myopathy.
[So] Source:Muscle Nerve;55(6):919-922, 2017 Jun.
[Is] ISSN:1097-4598
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Acyl-coenzyme A dehydrogenase 9 (ACAD9) has a role in mitochondrial complex I (CI) assembly. Only a few patients who carry ACAD9 mutations have been reported. They mainly present with severe hypertrophic cardiomyopathy, although a minority have only mild isolated myopathy. Although the secondary factors influencing disease severity have not been elucidated, conservation of CI assembly and residual enzymatic activity have been suggested as explanations for the mild phenotypes associated with ACAD9 mutations. METHODS: We report a novel homozygous ACAD9 mutation (c.1240C>T; p.Arg414Cys) in a 34-year-old woman who presented with non-progressive myopathy. RESULTS: We show that this ACAD9 mutation led to a severe defect in CI assembly in the patient's muscle. Furthermore, the impact of CI deficiency is confirmed by accumulation of mitochondrial DNA deletions. CONCLUSION: Our data suggest that a major defect of CI assembly is not responsible for a severe phenotype. Muscle Nerve 55: 919-922, 2017.
[Mh] Termos MeSH primário: Acil-CoA Desidrogenases/metabolismo
[Mh] Termos MeSH secundário: Acil-CoA Desidrogenases/genética
Adulto
Consanguinidade
Análise Mutacional de DNA
DNA Mitocondrial/genética
Complexo I de Transporte de Elétrons/genética
Complexo I de Transporte de Elétrons/metabolismo
Feminino
Seres Humanos
Doenças Musculares/genética
Doenças Musculares/patologia
Mutação/genética
[Pt] Tipo de publicação:CASE REPORTS
[Nm] Nome de substância:
0 (DNA, Mitochondrial); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.6.5.3 (Electron Transport Complex I)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160721
[St] Status:MEDLINE
[do] DOI:10.1002/mus.25262


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[PMID]:27871288
[Au] Autor:Bartha JL; Bugatto F; Fernández-Deudero Á; Fernández-Macías R; Perdomo G
[Ad] Endereço:Department of Obstetrics and Gynecology, University Hospital "La Paz", Madrid, Spain. jose.bartha@uam.es.
[Ti] Título:Tissue specific expression of human fatty acid oxidation enzyme genes in late pregnancy.
[So] Source:Lipids Health Dis;15(1):200, 2016 Nov 21.
[Is] ISSN:1476-511X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Abnormal fatty acid oxidation (FAO) is associated with maternal and fetal complications during pregnancy. The contribution of maternal and fetal tissues to FAO capacity during late pregnancy is important to understand the pathophysiology of pregnancy-associated complications. The aim of this study was to determine the expression levels of mitochondrial FAO enzymes in maternal and fetal tissues during late normal pregnancy. METHODS: We have measured by Real-time PCR the levels of long- and medium -chain acyl-CoA dehydrogenase (LCHAD and MCAD), two acyl-CoA dehydrogenases that catalyze the initial step in the mitochondrial FAO spiral. RESULTS: LCHAD and MCAD were expressed in maternal skeletal muscle, subcutaneous adipose tissue, placenta, and maternal and fetal blood cells. LCHAD gene expression was four- to 16-fold higher than MCAD gene expression in placenta, adipose tissue and skeletal muscle. In contrast, MCAD gene expression was ~5-fold higher in fetal blood than maternal blood (p = 0.02), whereas LCHAD gene expression was similar between fetal blood and maternal blood (p =0.91). CONCLUSIONS: LCHAD and MCAD are differentially expressed in maternal and fetal tissues during normal late pregnancy, which may represent a metabolic adaptation in response to physiological maternal dyslipidemia during late pregnancy.
[Mh] Termos MeSH primário: Acil-CoA Desidrogenases/genética
Ácidos Graxos/metabolismo
Feto/enzimologia
Expressão Gênica
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Especificidade de Órgãos
Gravidez
Terceiro Trimestre da Gravidez
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); EC 1.3.- (Acyl-CoA Dehydrogenases)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


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[PMID]:27791349
[Au] Autor:Peng H; Wei E; Wang J; Zhang Y; Cheng L; Ma H; Deng Z; Qu X
[Ad] Endereço:Key Laboratory of Combinatorial Biosynthesis and Drug Discovery Ministry of Education, School of Pharmaceutical Sciences, Wuhan University , 185 Donghu Road, Wuhan 430071, China.
[Ti] Título:Deciphering Piperidine Formation in Polyketide-Derived Indolizidines Reveals a Thioester Reduction, Transamination, and Unusual Imine Reduction Process.
[So] Source:ACS Chem Biol;11(12):3278-3283, 2016 12 16.
[Is] ISSN:1554-8937
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Piperidine and indolizidine are two basic units of alkaloids that are frequently observed in natural and synthetic compounds. Their biosynthesis in natural products is highly conserved and mostly derived from the incorporation of lysine cyclization products. Through in vitro reconstitution, we herein identified a novel pathway involving a group of polyketide-derived indolizidines, which comprises the processes of tandem two-electron thioester reduction, transamination, and imine reduction to convert acyl carrier protein (ACP)-tethered polyketide chains into the piperidine moieties of their indolizidine scaffolds. The enzymes that catalyze the imine reduction are distinct from previous known imine reductases, which have a fold of acyl-CoA dehydrogenase but do not require flavin for reduction. Our results not only provide a new way for the biosynthesis of the basic units of alkaloids but also show a novel class of imine reductases that may benefit the fields of biocatalysis and biomanufacturing.
[Mh] Termos MeSH primário: Indolizidinas/metabolismo
Piperidinas/metabolismo
Policetídeos/metabolismo
Streptomyces/enzimologia
[Mh] Termos MeSH secundário: Proteína de Transporte de Acila/metabolismo
Acil-CoA Desidrogenases/metabolismo
Vias Biossintéticas
Iminas/química
Iminas/metabolismo
Indolizidinas/química
Piperidinas/química
Policetídeos/química
Streptomyces/metabolismo
[Pt] Tipo de publicação:LETTER; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acyl Carrier Protein); 0 (Imines); 0 (Indolizidines); 0 (Piperidines); 0 (Polyketides); 67I85E138Y (piperidine); EC 1.3.- (Acyl-CoA Dehydrogenases)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170310
[Lr] Data última revisão:
170310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161104
[St] Status:MEDLINE


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[PMID]:27233227
[Au] Autor:Dewulf JP; Barrea C; Vincent MF; De Laet C; Van Coster R; Seneca S; Marie S; Nassogne MC
[Ad] Endereço:Université Catholique de Louvain, Cliniques Universitaires Saint-Luc, Service de Biochimie génétique, B-1200 Brussels, Belgium.
[Ti] Título:Evidence of a wide spectrum of cardiac involvement due to ACAD9 mutations: Report on nine patients.
[So] Source:Mol Genet Metab;118(3):185-9, 2016 Jul.
[Is] ISSN:1096-7206
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acyl-CoA dehydrogenase 9 (ACAD9) is a mitochondrial protein involved in oxidative phosphorylation complex I biogenesis. This protein also exhibits acyl-CoA dehydrogenase (ACAD) activity. ACAD9-mutated patients have been reported to suffer from primarily heart, muscle, liver, and nervous system disorders. ACAD9 mutation is suspected in cases of elevated lactic acid levels combined with complex I deficiency, and confirmed by ACAD9 gene analysis. At least 18 ACAD9-mutated patients have previously been reported, usually displaying severe cardiac involvement. We retrospectively studied nine additional patients from three unrelated families with a wide spectrum of cardiac involvement between the families as well as the patients from the same families. All patients exhibited elevated lactate levels. Deleterious ACAD9 mutations were identified in all patients except one for whom it was not possible to recover DNA. To our knowledge, this is one of the first reports on isolated mild ventricular hypertrophy due to ACAD9 mutation in a family with moderate symptoms during adolescence. This report also confirms that dilated cardiomyopathy may occur in conjunction with ACAD9 mutation and that some patients may respond clinically to riboflavin treatment. Of note, several patients suffered from patent ductus arteriosus (PDA), with one exhibiting a complex congenital heart defect. It is yet unknown whether these cardiac manifestations were related to ACAD9 mutation. In conclusion, this disorder should be suspected in the presence of lactic acidosis, complex I deficiency, and any cardiac involvement, even mild.
[Mh] Termos MeSH primário: Acil-CoA Desidrogenases/genética
Cardiopatias/genética
Ácido Láctico/sangue
Mutação
[Mh] Termos MeSH secundário: Acil-CoA Desidrogenases/metabolismo
Adulto
Criança
Feminino
Predisposição Genética para Doença
Cardiopatias/tratamento farmacológico
Seres Humanos
Lactente
Recém-Nascido
Masculino
Linhagem
Estudos Retrospectivos
Riboflavina/uso terapêutico
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
33X04XA5AT (Lactic Acid); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.99.- (ACAD9 protein, human); TLM2976OFR (Riboflavin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170829
[Lr] Data última revisão:
170829
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160529
[St] Status:MEDLINE


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[PMID]:27215383
[Au] Autor:Zurita Rendón O; Antonicka H; Horvath R; Shoubridge EA
[Ad] Endereço:Montreal Neurological Institute and Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
[Ti] Título:A Mutation in the Flavin Adenine Dinucleotide-Dependent Oxidoreductase FOXRED1 Results in Cell-Type-Specific Assembly Defects in Oxidative Phosphorylation Complexes I and II.
[So] Source:Mol Cell Biol;36(16):2132-40, 2016 Aug 15.
[Is] ISSN:1098-5549
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Complex I (NADH ubiquinone oxidoreductase) is a large multisubunit enzyme that catalyzes the first step in oxidative phosphorylation (OXPHOS). In mammals, complex I biogenesis occurs in a stepwise manner, a process that requires the participation of several nucleus-encoded accessory proteins. The FAD-dependent oxidoreductase-containing domain 1 (FOXRED1) protein is a complex I assembly factor; however, its specific role in the assembly pathway remains poorly understood. We identified a homozygous missense mutation, c.1308 G→A (p.V421M) in FOXRED1 in a patient who presented with epilepsy and severe psychomotor retardation. A patient myoblast line showed a severe reduction in complex I, associated with the accumulation of subassemblies centered around ∼340 kDa, and a milder decrease in complex II, all of which were rescued by retroviral expression of wild-type FOXRED1. Two additional assembly factors, AIFM1 and ACAD9, coimmunoprecipitated with FOXRED1, and all were associated with a 370-kDa complex I subassembly that, together with a 315-kDa subassembly, forms the 550-kDa subcomplex. Loss of FOXRED1 function prevents efficient formation of this midassembly subcomplex. Although we could not identify subassemblies of complex II, our results establish that FOXRED1 function is both broader than expected, involving the assembly of two flavoprotein-containing OXPHOS complexes, and cell type specific.
[Mh] Termos MeSH primário: Complexo II de Transporte de Elétrons/metabolismo
Complexo I de Transporte de Elétrons/metabolismo
Doenças Mitocondriais/genética
Chaperonas Moleculares/genética
Mutação de Sentido Incorreto
[Mh] Termos MeSH secundário: Acil-CoA Desidrogenases/metabolismo
Fator de Indução de Apoptose/metabolismo
Linhagem Celular
Predisposição Genética para Doença
Homozigoto
Seres Humanos
Mioblastos/citologia
Mioblastos/metabolismo
Multimerização Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIFM1 protein, human); 0 (Apoptosis Inducing Factor); 0 (FOXRED1 protein, human); 0 (Molecular Chaperones); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.5.1 (Electron Transport Complex II); EC 1.3.99.- (ACAD9 protein, human); EC 1.6.5.3 (Electron Transport Complex I)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160525
[St] Status:MEDLINE
[do] DOI:10.1128/MCB.00066-16


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[PMID]:26986205
[Au] Autor:Cuenca Mdel S; Roca A; Molina-Santiago C; Duque E; Armengaud J; Gómez-Garcia MR; Ramos JL
[Ad] Endereço:Abengoa Research, Abengoa, C/ Energía Solar 1, Palmas Altas, Sevilla, 41014, Spain.
[Ti] Título:Understanding butanol tolerance and assimilation in Pseudomonas putida BIRD-1: an integrated omics approach.
[So] Source:Microb Biotechnol;9(1):100-15, 2016 Jan.
[Is] ISSN:1751-7915
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pseudomonas putida BIRD-1 has the potential to be used for the industrial production of butanol due to its solvent tolerance and ability to metabolize low-cost compounds. However, the strain has two major limitations: it assimilates butanol as sole carbon source and butanol concentrations above 1% (v/v) are toxic. With the aim of facilitating BIRD-1 strain design for industrial use, a genome-wide mini-Tn5 transposon mutant library was screened for clones exhibiting increased butanol sensitivity or deficiency in butanol assimilation. Twenty-one mutants were selected that were affected in one or both of the processes. These mutants exhibited insertions in various genes, including those involved in the TCA cycle, fatty acid metabolism, transcription, cofactor synthesis and membrane integrity. An omics-based analysis revealed key genes involved in the butanol response. Transcriptomic and proteomic studies were carried out to compare short and long-term tolerance and assimilation traits. Pseudomonas putida initiates various butanol assimilation pathways via alcohol and aldehyde dehydrogenases that channel the compound to central metabolism through the glyoxylate shunt pathway. Accordingly, isocitrate lyase - a key enzyme of the pathway - was the most abundant protein when butanol was used as the sole carbon source. Upregulation of two genes encoding proteins PPUBIRD1_2240 and PPUBIRD1_2241 (acyl-CoA dehydrogenase and acyl-CoA synthetase respectively) linked butanol assimilation with acyl-CoA metabolism. Butanol tolerance was found to be primarily linked to classic solvent defense mechanisms, such as efflux pumps, membrane modifications and control of redox state. Our results also highlight the intensive energy requirements for butanol production and tolerance; thus, enhancing TCA cycle operation may represent a promising strategy for enhanced butanol production.
[Mh] Termos MeSH primário: Butanóis/metabolismo
Pseudomonas putida/metabolismo
[Mh] Termos MeSH secundário: Acetato-CoA Ligase/genética
Acetato-CoA Ligase/metabolismo
Acil-CoA Desidrogenases/genética
Acil-CoA Desidrogenases/metabolismo
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Proteômica
Pseudomonas putida/enzimologia
Pseudomonas putida/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Butanols); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 6.2.1.1 (Acetate-CoA Ligase)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160318
[St] Status:MEDLINE
[do] DOI:10.1111/1751-7915.12328


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[PMID]:26969249
[Au] Autor:Lu C; Zhang X; Jiang M; Bai L
[Ad] Endereço:State Key Laboratory of Microbial Metabolism and School of Life Sciences & Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China; Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
[Ti] Título:Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus.
[So] Source:Metab Eng;35:129-137, 2016 May.
[Is] ISSN:1096-7184
[Cp] País de publicação:Belgium
[La] Idioma:eng
[Ab] Resumo:The anticoccidial salinomycin is a polyketide produced by Streptomyces albus and requires malonyl-CoAs, methylmalonyl-CoAs, and ethylmalonyl-CoAs for the backbone assembly. Genome sequencing of S. albus DSM 41398 revealed a high percentage of genes involved in lipid metabolism, supporting the high salinomycin yield in oil-rich media. Seven PKS/PKS-NRPS gene clusters in the genome were found to be actively transcribed and had been individually deleted, which resulted in significantly improved salinomycin production. However, a combined deletion of PKS-NRPS-2 and PKS-6 showed no further improvement. Whereas the concentrations of malonyl-CoA and methylmalonyl-CoA were increased, the concentration of ethylmalonyl-CoA remained low in the mutants. An endogenous crotonyl-CoA reductase gene (ccr) was overexpressed in the ΔPKS-NRPS-2/ΔPKS-6 mutant, resulting in improved production. Combination of cluster deletions and over-expression of ccr gene led to an overall titer improvement of salinomycin from 0.60 to 6.60g/L. This engineering strategy can be implemented for various natural polyketides production.
[Mh] Termos MeSH primário: Policetídeos/metabolismo
Piranos/metabolismo
Streptomyces
[Mh] Termos MeSH secundário: Acil Coenzima A/genética
Acil Coenzima A/metabolismo
Acil-CoA Desidrogenases/biossíntese
Acil-CoA Desidrogenases/genética
Proteínas de Bactérias/biossíntese
Proteínas de Bactérias/genética
Engenharia Metabólica
Policetídeo Sintases/biossíntese
Policetídeo Sintases/genética
Streptomyces/genética
Streptomyces/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Acyl Coenzyme A); 0 (Bacterial Proteins); 0 (Polyketides); 0 (Pyrans); 62UXS86T64 (salinomycin); 79956-01-7 (Polyketide Synthases); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.1.8 (acyl-CoA dehydrogenase (NADP+))
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160313
[St] Status:MEDLINE


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[PMID]:26826406
[Au] Autor:Leslie N; Wang X; Peng Y; Valencia CA; Khuchua Z; Hata J; Witte D; Huang T; Bove KE
[Ad] Endereço:Divisions of Human Genetics, Gastroenterology, and Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
[Ti] Título:Neonatal multiorgan failure due to ACAD9 mutation and complex I deficiency with mitochondrial hyperplasia in liver, cardiac myocytes, skeletal muscle, and renal tubules.
[So] Source:Hum Pathol;49:27-32, 2016 Mar.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Complex I deficiency causes Leigh syndrome, fatal infant lactic acidosis, and neonatal cardiomyopathy. Mutations in more than 100 nuclear DNA and mitochondrial DNA genes miscode for complex I subunits or assembly factors. ACAD9 is an acyl-CoA dehydrogenase with a novel function in assembly of complex I; biallelic mutations cause progressive encephalomyopathy, recurrent Reye syndrome, and fatal cardiomyopathy. We describe the first autopsy in fatal neonatal lethal lactic acidosis due to mutations in ACAD9 that reduced complex I activity. We identified mitochondrial hyperplasia in cardiac myocytes, diaphragm muscle, and liver and renal tubules in formalin-fixed, paraffin-embedded tissue using immunohistochemistry for mitochondrial antigens. Whole-exome sequencing revealed compound heterozygous variants in the ACAD9 gene: c.187G>T (p.E63*) and c.941T>C (p.L314P). The nonsense mutation causes late infantile lethality; the missense variant is novel. Autopsy-derived fibroblasts had reduced complex I activity (53% of control) with normal activity in complexes II to IV, similar to reported cases of ACAD9 deficiency.
[Mh] Termos MeSH primário: Acidose Láctica/diagnóstico
Acidose/diagnóstico
Acil-CoA Desidrogenase/deficiência
Acil-CoA Desidrogenases/genética
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico
Cardiomiopatia Hipertrófica/diagnóstico
Códon sem Sentido
Diafragma/patologia
Complexo I de Transporte de Elétrons/deficiência
Túbulos Renais/patologia
Doença de Leigh/diagnóstico
Mitocôndrias Cardíacas/patologia
Mitocôndrias Hepáticas/patologia
Mitocôndrias Musculares/patologia
Doenças Mitocondriais/diagnóstico
Insuficiência de Múltiplos Órgãos/diagnóstico
Debilidade Muscular/diagnóstico
[Mh] Termos MeSH secundário: Acidose/enzimologia
Acidose/genética
Acidose/patologia
Acidose Láctica/enzimologia
Acidose Láctica/genética
Acidose Láctica/patologia
Acil-CoA Desidrogenase/genética
Acil-CoA Desidrogenases/deficiência
Erros Inatos do Metabolismo dos Aminoácidos/enzimologia
Erros Inatos do Metabolismo dos Aminoácidos/genética
Erros Inatos do Metabolismo dos Aminoácidos/patologia
Autopsia
Cardiomiopatia Hipertrófica/enzimologia
Cardiomiopatia Hipertrófica/genética
Cardiomiopatia Hipertrófica/patologia
Causas de Morte
Células Cultivadas
Análise Mutacional de DNA
DNA Mitocondrial/genética
Diafragma/enzimologia
Complexo I de Transporte de Elétrons/genética
Evolução Fatal
Fibroblastos/enzimologia
Fibroblastos/patologia
Predisposição Genética para Doença
Seres Humanos
Hiperplasia
Imuno-Histoquímica
Recém-Nascido
Túbulos Renais/enzimologia
Doença de Leigh/enzimologia
Doença de Leigh/genética
Doença de Leigh/patologia
Masculino
Mitocôndrias Cardíacas/enzimologia
Mitocôndrias Hepáticas/enzimologia
Mitocôndrias Musculares/enzimologia
Doenças Mitocondriais/enzimologia
Doenças Mitocondriais/genética
Doenças Mitocondriais/patologia
Insuficiência de Múltiplos Órgãos/enzimologia
Insuficiência de Múltiplos Órgãos/genética
Insuficiência de Múltiplos Órgãos/patologia
Debilidade Muscular/enzimologia
Debilidade Muscular/genética
Debilidade Muscular/patologia
Fenótipo
Transfecção
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Codon, Nonsense); 0 (DNA, Mitochondrial); EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.8.7 (Acyl-CoA Dehydrogenase); EC 1.3.99.- (ACAD9 protein, human); EC 1.6.5.3 (Electron Transport Complex I)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:160131
[Lr] Data última revisão:
160131
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160131
[St] Status:MEDLINE


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[PMID]:26669660
[Au] Autor:Collet M; Assouline Z; Bonnet D; Rio M; Iserin F; Sidi D; Goldenberg A; Lardennois C; Metodiev MD; Haberberger B; Haack T; Munnich A; Prokisch H; Rötig A
[Ad] Endereço:Departments of Pediatric, Cardiology and Genetics and INSERM U1163, Université Paris Descartes-Sorbonne Paris Cité, Institut Imagine, Hôpital Necker-Enfants-Malades, Paris, France.
[Ti] Título:High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.
[So] Source:Eur J Hum Genet;24(8):1112-6, 2016 Aug.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Acyl-CoA dehydrogenase family, member 9 (ACAD9) mutation is a frequent, usually fatal cause of early-onset cardiac hypertrophy and mitochondrial respiratory chain complex I deficiency in early childhood. We retrospectively studied a series of 20 unrelated children with cardiac hypertrophy and isolated complex I deficiency and identified compound heterozygosity for missense, splice site or frame shift ACAD9 variants in 8/20 patients (40%). Age at onset ranged from neonatal period to 9 years and 5/8 died in infancy. Heart transplantation was possible in 3/8. Two of them survived and one additional patient improved spontaneously. Importantly, the surviving patients later developed delayed-onset neurologic or muscular symptoms, namely cognitive impairment, seizures, muscle weakness and exercise intolerance. Other organ involvement included proximal tubulopathy, renal failure, secondary ovarian failure and optic atrophy. We conclude that ACAD9 mutation is the most frequent cause of cardiac hypertrophy and isolated complex I deficiency. Heart transplantation in children surviving neonatal period should be considered with caution, as delayed-onset muscle and brain involvement of various severity may occur, even if absent prior to transplantation.
[Mh] Termos MeSH primário: Acil-CoA Desidrogenases/genética
Cardiomegalia/genética
Complexo I de Transporte de Elétrons/deficiência
Doenças Mitocondriais/genética
Taxa de Mutação
[Mh] Termos MeSH secundário: Acil-CoA Desidrogenases/metabolismo
Cardiomegalia/patologia
Células Cultivadas
Criança
Pré-Escolar
Complexo I de Transporte de Elétrons/genética
Feminino
Mutação da Fase de Leitura
Seres Humanos
Lactente
Masculino
Doenças Mitocondriais/patologia
Mutação de Sentido Incorreto
Síndrome
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.3.- (Acyl-CoA Dehydrogenases); EC 1.3.99.- (ACAD9 protein, human); EC 1.6.5.3 (Electron Transport Complex I)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151217
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2015.264



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