Link Found Between Mitochondrial DNA and Inflammation Regulation

Researchers at the Max Planck Institute for Biology of Aging and the CECAD Cluster of Excellence in Aging Research have identified a link between mitochondrial genetic material and cellular metabolism. The team found that when the cell's DNA building blocks are in short supply, mitochondria release their genetic material and trigger inflammation. Their study was published in Nature. 

To answer the question of when mitochondria release their DNA, the researchers focused on the mitochondrial protein YME1L, which owes its name to yeast mutants that release their mitochondrial DNA—yeast mitochondrial escape 1. 

"In cells lacking YME1L, we observed the release of mitochondrial DNA into the cell interior and a related immune response in the cells,” said Thomas MacVicar, one of the study's two first authors. Closer examination revealed a direct link to the building blocks of DNA. "If the cells lack YME1L, there is a deficiency of DNA building blocks inside the cell,” Thomas MacVicar describes. "This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates similar inflammatory reactions as it does during a bacterial or viral infection. If we add DNA building blocks to the cells from the outside, that also stops the inflammation."

The discovered link between the cellular inflammatory response and the metabolism of DNA building blocks could have far-reaching consequences, explains Thomas MacVicar, "Some viral inhibitors stop the production of certain DNA building blocks, thereby triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this, contributing to the effect of these inhibitors." Several aging-associated inflammatory diseases, including cardiac and neurodegenerative diseases, as well as obesity and cancer, are linked to mitochondrial DNA. The authors hope that modulating the metabolism of DNA building blocks will offer new therapeutic opportunities in such diseases.