Scientists Found a New Epigenetic Factor Preventing Inherited Diseases
Researchers at the University of Queensland have identified a crucial mechanism in mitochondrial DNA (mtDNA) that helps regulate the inheritance of disease-causing mutations. This mechanism involves a chemical modification called adenine methylation (6mA), which the study found to be vital in controlling mutation accumulation in mtDNA. Mitochondrial DNA, inherited exclusively from mothers, is essential for cellular energy production and is known to mutate as we age, contributing to diseases such as dementia, cancer, and diabetes.
The research, led by Dr. Anne Hahn and Associate Professor Steven Zuryn at the Queensland Brain Institute, focused on understanding how 6mA impacts the stability of mtDNA across various species, including humans. The team discovered that 6mA is regulated by two specific enzymes, which they identified through experiments using the model organism Caenorhabditis elegans and lab-grown human cells. These enzymes control the addition of the 6mA modification, which acts as a safeguard against the accumulation of harmful mutations.
When the researchers experimentally removed the 6mA modification from mtDNA, they observed a significant increase in the number of mutations, suggesting that 6mA plays a crucial role in maintaining the integrity of the mitochondrial genome. Without 6mA, mutations accumulate rapidly, leading to potential hereditary transmission of these harmful changes to offspring. This finding provides direct evidence that 6mA is a key factor in preventing the passage of disease-related mutations through mtDNA.
Mitochondrial DNA differs from nuclear DNA in that it does not undergo the same level of recombination and repair, making it particularly vulnerable to mutations that can be passed from mother to child. The discovery that 6mA can mitigate this risk offers a new approach to understanding the inheritance of mitochondrial diseases. Enhancing 6mA levels in mtDNA could potentially slow the progression of age-related diseases by reducing the accumulation of mutations over time.
The study’s findings bridge the gap between genetics and epigenetics, showing that chemical modifications like 6mA can influence not only gene expression but also the stability and inheritance of the genetic material itself. The implications of this research are significant, as they suggest a possible pathway for developing therapies aimed at reducing the transmission of mitochondrial mutations and thereby preventing related diseases in future generations.
The research conducted by Dr. Hahn, Dr. Zuryn, and their team has been published in the journal Cell Metabolism, adding a crucial piece to the puzzle of how genetic and epigenetic factors work together to protect against the inheritance of harmful mutations.
Source:
Hahn, A., et al. (2024) Misregulation of mitochondrial 6mA promotes the propagation of mutant mtDNA and causes aging in C. elegans. Cell Metabolism. doi.org/10.1016/j.cmet.2024.07.020.
Topics: Aging & Longevity
