Department of Clinical Diagnostics, Vitebsk State Academy of Veterinary Medicine, 210026 Vitebsk, Belarus.
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow, Russia.
Int J Mol Sci. 2021 Jun 23;22(13):6733. doi: 10.3390/ijms22136733.
Diabetes mellitus and related disorders significantly contribute to morbidity and mortality worldwide. Despite the advances in the current therapeutic methods, further development of anti-diabetic therapies is necessary. Mitochondrial dysfunction is known to be implicated in diabetes development. Moreover, specific types of mitochondrial diabetes have been discovered, such as MIDD (maternally inherited diabetes and deafness) and DAD (diabetes and Deafness). Hereditary mitochondrial disorders are caused by certain mutations in the mitochondrial DNA (mtDNA), which encodes for a substantial part of mitochondrial proteins and mitochondrial tRNA necessary for mitochondrial protein synthesis. Study of mtDNA mutations is challenging because the pathogenic phenotype associated with such mutations depends on the level of its heteroplasmy (proportion of mtDNA copies carrying the mutation) and can be tissue-specific. Nevertheless, modern sequencing methods have allowed describing and characterizing a number of mtDNA mutations associated with human disorders, and the list is constantly growing. In this review, we provide a list of mtDNA mutations associated with diabetes and related disorders and discuss the mechanisms of their involvement in the pathology development.
糖尿病及其相关疾病在全球范围内显著导致发病率和死亡率。尽管目前的治疗方法有所进步，但仍有必要进一步开发抗糖尿病疗法。线粒体功能障碍已知与糖尿病的发展有关。此外，已经发现了特定类型的线粒体糖尿病，如 MIDD（母系遗传性糖尿病和耳聋）和 DAD（糖尿病和耳聋）。遗传性线粒体疾病是由线粒体 DNA（mtDNA）中的某些突变引起的，这些突变编码了线粒体蛋白的很大一部分和线粒体 tRNA，这些 tRNA 对于线粒体蛋白合成是必需的。研究 mtDNA 突变具有挑战性，因为与这些突变相关的致病表型取决于其异质性（携带突变的 mtDNA 拷贝的比例）的水平，并且可能具有组织特异性。然而，现代测序方法已经允许描述和表征与人类疾病相关的许多 mtDNA 突变，并且该列表还在不断增加。在这篇综述中，我们提供了与糖尿病和相关疾病相关的 mtDNA 突变列表，并讨论了它们参与病理发展的机制。
