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

• DOI: 10.1038/srep10480
• Publication Date: 2015-05-27T13:40:22Z
• Authors: 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
• Keywords: Exercise intolerance

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