The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes.
The Role of Mitochondrial Mutations and Chronic Inflammation in Diabetes.
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线粒体突变和慢性炎症在糖尿病中的作用。
DOI：
10.3390/ijms22136733
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发表时间：
2021-06-23
影响因子：
5.6
通讯作者：
Orekhov AN
中科院分区：
文献类型：
--
作者：
Dabravolski SA;Orekhova VA;Baig MS;Bezsonov EE;Starodubova AV;Popkova TV;Orekhov AN
糖尿病及相关疾病是全球发病率和死亡率的重要原因。尽管目前的治疗方法取得了进展，但仍需要进一步开发抗糖尿病疗法。已知线粒体功能障碍与糖尿病发展有关。此外，还发现了特定类型的线粒体糖尿病，如MIDD（母系遗传的糖尿病和耳聋）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，所述线粒体DNA编码线粒体蛋白质的大部分和线粒体蛋白质合成所必需的线粒体tRNA。mtDNA突变的研究具有挑战性，因为与此类突变相关的致病表型取决于其异质性水平（携带突变的mtDNA拷贝的比例），并且可以是组织特异性的。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一些mtDNA突变，并且该列表正在不断增长。本文综述了与糖尿病及相关疾病相关的线粒体DNA突变，并讨论了它们参与糖尿病病理发展的机制。
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.
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