Research: Mitochondrial DNA mutations associated with heart disease risk

Aug 05, 2022

Washington (US), August 5 (ANI): During a recent study researchers have discovered how mitochondrial function, and dysfunction, play critical roles in numerous diseases, and even ageing. In a new study published in the online issue of Immunity, scientists at the University of California San Diego School of Medicine and Salk Institute for Biological Studies report a surprising link between mitochondria, inflammation, and DNMT3A and TET2, a pair of genes that normally help regulate blood cell growth, but when mutated, are associated with an increased risk of atherosclerosis. It is estimated approximately half of Americans between the ages of 45 and 84 have atherosclerosis, which is the single leading cause of death in the United States and westernized nations. Inside mitochondria resides a unique subset of the cell's DNA that must be organized and condensed correctly to sustain normal function. They discovered that experimentally reducing the expression of DNMT3A or TET2 in normal blood cells produced similar results to blood cells that had loss of function mutations and to blood cells from atherosclerosis patients. "We discovered that DNMT3A and TET2 mutations prevent their ability to bind and activate the TFAM gene, Missing or reducing this binding activity leads to mitochondrial DNA release and overactive mitochondrial inflammation response. We believe this may exacerbate plaque buildup in atherosclerosis." Shadel said the findings broaden and deepen understanding of mitochondrial function and their role in disease. "It's very exciting to see our discovery on TFAM depletion causing mitochondrial DNA stress and inflammation now have direct relevance for a disease like atherosclerosis," said Shadel. "Ever since we revealed this pathway, there has been an explosion of interest in mitochondria being involved in inflammation and many reports linking mitochondrial DNA release to other clinical contexts."