Neurite growth could be impaired by ETFDH mutation but restored by mitochondrial cofactors.
Muscle Nerve
; 56(3): 479-485, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-27935074
ABSTRACT
INTRODUCTION:
c.250G>A (p.Ala84Thr) in ETFDH is the most common mutation that causes later-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD) in the southern Chinese population. No functional study has targeted this mutation.METHODS:
Using cells expressing ETFDH-wild-type (WT) or ETFDH-mutant (p.Ala84Thr), reactive oxygen species (ROS) production and neurite length were analyzed, followed by pathomechanism exploration and drug screening.RESULTS:
Increased ROS production and marked neurite shortening were observed in the cells expressing the ETFDH-mutant, compared with WT. Further studies demonstrated that suberic acid, an accumulated intermediate metabolite in MADD, could significantly impair neurite outgrowth of NSC34 cells, but neurite shortening could be restored by supplementation with carnitine, riboflavin, or Coenzyme Q10.CONCLUSIONS:
Neurite shortening caused by the c.250G>A mutation in ETFDH suggests that neural defects could be underdiagnosed in human patients with MADD. This impairment might be treatable with mitochondrial cofactor supplementation. Muscle Nerve 56 479-485, 2017.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Flavoproteínas Transferidoras de Elétrons
/
Crescimento Neuronal
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Oxirredutases atuantes sobre Doadores de Grupo CH-NH
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Proteínas Ferro-Enxofre
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Mitocôndrias
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Mutação
Limite:
Humans
Idioma:
En
Revista:
Muscle Nerve
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Taiwan