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学科主题: 临床医学
题名:
Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation
作者: 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
发表日期: 2015-05-27
DOI: 10.1038/srep10480
卷: 5
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Multidisciplinary Sciences
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
项目资助者: Chinese National Science Foundation ; Zhejiang Provincial Natural Science Foundation of China ; Start Foundation of Wenzhou Medical University
WOS记录号: WOS:000355536000001
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67184
Appears in Collections:北京大学第一临床医学院_儿科_期刊论文

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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

Recommended Citation:
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.
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