Shortage of DNA building blocks in cell releases mitochondrial DNA – sciencedaily

Mitochondria are the energy providers of our body cells. These tiny cellular components have their own genetic material, which triggers an inflammatory response when released inside the cell. The reasons for this release are not yet known, but some heart and neurodegenerative diseases as well as the aging process are linked to the mitochondrial genome. Researchers from the Max Planck Institute for the Biology of Aging and the CECAD Center of Excellence in Aging Research have studied the reasons for the release of mitochondrial genetic material and have found a direct link with cell metabolism: when The building blocks of the cell’s DNA are scarce, the mitochondria release their genetic material and trigger inflammation. Researchers hope to find new therapeutic approaches by influencing this metabolic pathway.

Our body needs energy – for every metabolic process, every movement and to breathe. This energy is produced in tiny components of our body cells, the so-called mitochondria. Unlike other cellular components, mitochondria have their own genetic material, mitochondrial DNA. However, in some situations, the mitochondria release their DNA inside the cell, causing the cell’s own immune system to react and being associated with various diseases as well as the aging process. The reasons for the release of mitochondrial DNA are not yet known.

Shortage of DNA building blocks triggers inflammatory response

To answer the question of when mitochondria release their DNA, researchers at the Max Planck Institute for the Biology of Aging focused on the mitochondrial protein YME1L, which is named after yeast mutants that release their mitochondrial DNA – yeast mitochondrial escape 1. “In cells lacking YME1L, we observed the release of mitochondrial DNA into the interior of the cell and a related immune response in the cells,” said Thomas MacVicar, one of the first two study authors. Further examination revealed a direct link to the building blocks of DNA. “If cells lack YME1L, there is a deficiency of DNA building blocks within the cell. cell ”, describes Thomas MacVicar.“ This deficiency triggers the release of mitochondrial DNA, which in turn causes an inflammatory response in the cell: the cell stimulates inflammatory reactions similar to those of ‘a bacterial or viral infection. If we add the building blocks of DNA to cells from the outside, it also stops the inflammation. “

New therapeutic approaches based on the metabolism of the building blocks of DNA

The link discovered between the cellular inflammatory response and the metabolism of the building blocks of DNA could have considerable consequences, explains Thomas MacVicar: “Certain viral inhibitors stop the production of certain building blocks of DNA, thus triggering an inflammatory response. The release of mitochondrial DNA could be a crucial factor in this regard, contributing to the effect of these inhibitors. “Several inflammatory diseases associated with aging, including heart and neurodegenerative diseases, as well as obesity and cancer, are linked to mitochondrial DNA. The authors hope that modulation of the metabolism of DNA building blocks will provide additional benefits. new therapeutic opportunities in these diseases.

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