Chen 2020 Mol Genet Genomic Med

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Chen D, Zhao Q, Xiong J, Lou X, Han Q, Wei X, Xie J, Li X, Zhou H, Shen L, Yang Y, Fang H, Lyu J (2020) Systematic analysis of a mitochondrial disease-causing ND6 mutation in mitochondrial deficiency. Mol Genet Genomic Med 8:e1199.

» PMID: 32162843 Open Access

Chen Deyu, Zhao Qiongya, Xiong Jingting, Lou Xiaoting, Han Qinxia, Wei Xiujuan, Xie Jie, Li Xueyun, Zhou Huaibin, Shen Lijun, Yang Yanling, Fang Hezhi, Lyu Jianxin (2020) Mol Genet Genomic Med

Abstract: The m.14487T>C mutation is recognized as a diagnostic mutation of mitochondrial disease during the past 16 years, emerging evidence suggests that mutant loads of m.14487T>C and disease phenotype are not closely correlated.

Immortalized lymphocytes were generated by coculturing the Epstein-Barr virus and lymphocytes from m.14487T>C carrier Chinese patient with Leigh syndrome. Fifteen cytoplasmic hybrid (cybrid) cell lines were generated by fusing mtDNA lacking 143B cells with platelets donated by patients. Mitochondrial function was systematically analyzed at transcriptomic, metabolomic, and biochemical levels.

Unlike previous reports, we found that the assembly of mitochondrial respiratory chain complexes, mitochondrial respiration, and mitochondrial OXPHOS function was barely affected in cybrid cells carrying homoplastic m.14487T>C mutation. Mitochondrial dysfunction associated transcriptomic and metabolomic reprogramming were not detected in cybrid carrying homoplastic m.14487T>C. However, we found that mitochondrial function was impaired in patient-derived immortalized lymphocytes.

Our data revealed that m.14487T>C mutation is insufficient to cause mitochondrial deficiency; additional modifier genes may be involved in m.14487T>C-associated mitochondrial disease. Our results further demonstrated that a caution should be taken by solely use of m.14487T>C mutation for molecular diagnosis of mitochondrial disease.

© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

Keywords: Cybrids, Mitochondrial disease, mtDNA mutation, Transcriptome and metabolic analyses Bioblast editor: Plangger M


Labels: MiParea: Respiration, mtDNA;mt-genetics, Patients 

Stress:Mitochondrial disease  Organism: Human  Tissue;cell: Lymphocyte  Preparation: Intact cells 


Coupling state: LEAK, ROUTINE 

HRR: Oxygraph-2k 

2020-03