Department of Plastic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215006, China.
Department of Plastic and Burn Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
J Diabetes Res. 2020 Jan 30;2020:2057187. doi: 10.1155/2020/2057187. eCollection 2020.
We report here the clinical, genetic, and molecular characteristics of type 2 diabetes in a Chinese family. There are differences in the severity and age of onset in diabetes among these families. By molecular analysis of the complete mitochondrial genome in this family, we identified the homoplasmic m.15897G>A mutation underwent sequence analysis of whole mitochondrial DNA genome, which localized at conventional position ten of tRNA, and distinct sets of mtDNA polymorphisms belonging to haplogroup D4b1. This mutation has been implicated to be important for tRNA identity and stability. Using cybrid cell models, the decreased efficiency of mitochondrial tRNA levels caused by the m.15897G>A mutation results in respiratory deficiency, protein synthesis and assembly, mitochondrial ATP synthesis, and mitochondrial membrane potential. These mitochondrial dysfunctions caused an increase in the production of reactive oxygen species in the mutant cell lines. These data provide a direct evidence that a novel tRNA mutation was associated with T2DM. Thus, our findings provide a new insight into the understanding of pathophysiology of maternally inherited diabetes.
我们在此报道了一个中国家庭 2 型糖尿病的临床、遗传和分子特征。这些家族中糖尿病的严重程度和发病年龄存在差异。通过对该家族完整线粒体基因组的分子分析，我们发现了同型质 m.15897G>A 突变，对整个线粒体 DNA 基因组进行了序列分析，该突变位于 tRNA 的常规位置十，并且存在一组属于 D4b1 单倍群的独特 mtDNA 多态性。该突变被认为对 tRNA 的身份和稳定性很重要。使用细胞杂交模型，m.15897G>A 突变导致线粒体 tRNA 水平的效率降低，从而导致呼吸缺陷、蛋白质合成和组装、线粒体 ATP 合成和线粒体膜电位。这些线粒体功能障碍导致突变细胞系中活性氧的产生增加。这些数据提供了直接证据，表明一种新的 tRNA 突变与 T2DM 有关。因此，我们的发现为理解母系遗传糖尿病的病理生理学提供了新的见解。
