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学科主题临床医学
Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation
Fang, Hezhi1; Shi, Hao1; Li, Xiyuan2; Sun, Dayan1; Li, Fengjie1; Li, Bin1; Ding, Yuan2; Ma, Yanyan2; Liu, Yupeng2; Zhang, Yao2; Shen, Lijun1; Bai, Yidong3; Yang, Yanling2; Lu, Jianxin1
刊名SCIENTIFIC REPORTS
2015-05-27
DOI10.1038/srep10480
5
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者Chinese National Science Foundation ; Zhejiang Provincial Natural Science Foundation of China ; Start Foundation of Wenzhou Medical University ; Chinese National Science Foundation ; Zhejiang Provincial Natural Science Foundation of China ; Start Foundation of Wenzhou Medical University
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]RESPIRATORY COMPLEX-I ; CYTOCHROME-C-OXIDASE ; NADH DEHYDROGENASE ; ASSEMBLY FACTORS ; LEIGH-SYNDROME ; MEMBRANE ARM ; HUMAN-CELLS ; DNA ; SUBUNIT ; GENE
英文摘要

The aim of this study was to evaluate the contribution of mitochondrial DNA (mtDNA) mutations in oxidative phosphorylation (OXPHOS) deficiency. The complete mitochondrial genomes of 41 families with OXPHOS deficiency were screened for mutations. Mitochondrial functional analysis was then performed in primary and cybrid cells containing candidate mutations identified during the screening. A novel mitochondrial NADH dehydrogenase 5 (ND5) m.12955A > G mutation was identified in a patient with exercise intolerance and developmental delay. A biochemical analysis revealed deficiencies in the activity of complex I (NADH: quinone oxidoreductase) and IV (cytochrome c oxidase) of this patient. Defects in complexes I and IV were confirmed in transmitochondrial cybrid cells containing the m.12955A > G mutation, suggesting that this mutation impairs complex I assembly, resulting in reduced stability of complex IV. Further functional investigations revealed that mitochondria with the m.12955A > G mutation exhibited lower OXPHOS coupling respiration and adenosine triphosphate (ATP) generation. In addition, the cytotoxic effects, determined as reactive oxygen species (ROS) and lactate levels in the present study, increased in the cells carrying a higher m.12955A > G mutant load. In conclusion, we identified m.12955A > G as a mitochondrial disease-related mutation. Therefore, screening of m.12955A > G is advised for the diagnosis of patients with mitochondrial disease.

语种英语
所属项目编号81101506 ; 81471097 ; LQ15H070005
资助者Chinese National Science Foundation ; Zhejiang Provincial Natural Science Foundation of China ; Start Foundation of Wenzhou Medical University ; Chinese National Science Foundation ; Zhejiang Provincial Natural Science Foundation of China ; Start Foundation of Wenzhou Medical University
WOS记录号WOS:000355536000001
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67184
专题北京大学第一临床医学院_儿科
作者单位1.Wenzhou Med Univ, Coll Lab Med & Life Sci, Zhejiang Prov Key Lab Med Genet, Key Lab Lab Med,Minist Educ, Wenzhou 325035, Zhejiang, Peoples R China
2.Peking Univ, Hosp 1, Dept Pediat, Beijing 100034, Peoples R China
3.Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA
推荐引用方式
GB/T 7714
Fang, Hezhi,Shi, Hao,Li, Xiyuan,et al. Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation[J]. SCIENTIFIC REPORTS,2015,5.
APA Fang, Hezhi.,Shi, Hao.,Li, Xiyuan.,Sun, Dayan.,Li, Fengjie.,...&Lu, Jianxin.(2015).Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation.SCIENTIFIC REPORTS,5.
MLA Fang, Hezhi,et al."Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation".SCIENTIFIC REPORTS 5(2015).
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