The role of mitochondrial-related nuclear genes in age-related common disease

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.