Human Aging Research Institute, Nanchang University, Nanchang 330031, China; Wenzhou Key Laboratory of Birth Defects, Wenzhou Central Hospital, Wenzhou, Zhejiang 325000, China.
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Mitochondrion. 2020 Jul;53:38-47. doi: 10.1016/j.mito.2020.04.012. Epub 2020 Apr 30.
Mitochondria are critical organelles that provide energy as ATP to the cell. Besides 37 genes encoded by mitochondrial genome, it has been estimated that over 1500 nuclear genes are required for mitochondrial structure and function. Thus, mutations of many genes in the nuclear genome cause dysfunction of mitochondria that can lead to many severe conditions. Mitochondrial dysfunction often results in reduced ATP synthesis, higher levels of reactive oxygen species (ROS), imbalanced mitochondrial dynamics, and other detrimental effects. In addition to rare primary mitochondrial disorders, these mitochondrial-related genes are often associated with many common diseases. For example, in neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington disease, mitochondrialand energy metabolism abnormalities can greatly affect brain function. Cancer cells are also known to exhibit repressed mitochondrial ATP production in favor of glycolysis, which fuels the aggressive proliferation and metastasis of tumor tissues, leading many to speculate on a possible relationship between compromised mitochondrial function and cancer. The association between mitochondrial dysfunction and diabetes is also unsurprising, given the organelle's crucial role in cellular energy utilization. Here, we will discuss the multiple lines of evidence connecting mitochondrial dysfunction associated with mitochondria-related nuclear genes to many of the well-known disease genes that also underlie common disease.
线粒体是为细胞提供能量（以 ATP 的形式）的重要细胞器。除了线粒体基因组编码的 37 个基因外，据估计，有超过 1500 个核基因对于线粒体的结构和功能是必需的。因此，核基因组中许多基因的突变会导致线粒体功能障碍，从而导致许多严重的疾病。线粒体功能障碍通常导致 ATP 合成减少、活性氧（ROS）水平升高、线粒体动力学失衡和其他有害影响。除了罕见的原发性线粒体疾病外，这些与线粒体相关的基因通常与许多常见疾病有关。例如，在帕金森病、阿尔茨海默病和亨廷顿病等神经退行性疾病中，线粒体和能量代谢异常会极大地影响大脑功能。众所周知，癌细胞也会抑制线粒体产生 ATP，转而促进糖酵解，为肿瘤组织的侵袭性增殖和转移提供燃料，这使得许多人推测线粒体功能受损与癌症之间可能存在关联。鉴于线粒体在细胞能量利用中的关键作用，线粒体功能障碍与糖尿病之间的关联也不足为奇。在这里，我们将讨论将与线粒体相关的核基因相关的线粒体功能障碍与许多已知的疾病基因联系起来的多种证据，这些疾病基因也是许多常见疾病的基础。
