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Neurite growth could be impaired by ETFDH mutation but restored by mitochondrial cofactors
Author(s) -
Liang WenChen,
Lin YenFong,
Liu TingYuan,
Chang ShinCheng,
Chen BaiHsiun,
Nishino Ichizo,
Jong YuhJyh
Publication year - 2017
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.25501
Subject(s) - neurite , cofactor , mutation , mitochondrion , mitochondrial dna , genetics , biology , microbiology and biotechnology , gene , biochemistry , in vitro , enzyme
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