Exercise intolerance and developmental delay associated with a novel mitochondrial ND5 mutation

Hezhi Fang, Hao Shi, Xiyuan Li, Dayan Sun, Fengjie Li, Bin Li, Yuan Ding, Yanyan Ma, Yupeng Liu, Yao Zhang, Lijun Shen, Yidong Bai, Yanling Yang, Jianxin Lu

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


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.

Original languageEnglish (US)
Article number10480
JournalScientific reports
StatePublished - May 27 2015

ASJC Scopus subject areas

  • General


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