Mitochondria (illustration) have their own DNA, which they expel into their environment if the molecules don’t meet their standards.
Credit: Kateryna Kon/Science Photo Library
The cellular batteries known as mitochondria sometimes release DNA into their surroundings, contributing to inflammation during ageing. A recent study in mice reveals that this happens because mitochondria are discarding ‘tainted’ DNA1.
Researchers discovered that in aging mice with kidney inflammation, strands of mitochondrial DNA (mtDNA) had an excess of specific nucleotides — building blocks of DNA — that can cause damage. This imbalance led the mitochondria to expel the faulty DNA fragments into the cytosol, the cell’s fluid, triggering critical inflammatory pathways linked to ageing.
This study is groundbreaking because it clarifies why and how mitochondria eliminate their DNA, according to Timothy Shutt, a medical geneticist at the University of Calgary. This understanding could shed light on mitochondria’s role in inflammageing — the chronic inflammation that can occur with age, adds Shutt.
The findings were published on September 24 in Nature1.
Out with the rubbish
Mitochondria, the energy-producing powerhouses of our cells, possess their own genome. When mtDNA becomes damaged, mitochondria eject it into the cytosol. This often occurs if certain nucleotide levels become too high or too low.
This problem can stem from certain medications and is also observed in aging cells. However, the precise mechanism by which this nucleotide imbalance triggers mtDNA release and contributes to inflammageing had remained unclear, as explained by Thomas Langer, a cell biologist at the Max Planck Institute for Biology of Ageing in Cologne, Germany.
To investigate, Langer and his team studied mice engineered to lack an enzyme named MGME1, which is vital for accurate mitochondrial DNA replication. As these mice age, their kidneys typically become inflamed, making them valuable models for studying inflammation.
Summary: This article discusses recent findings about mitochondria, the energy producers in our cells, which sometimes release defective DNA that can contribute to inflammation and aging. Researchers discovered that in aging mice, certain nucleotide imbalances within mitochondrial DNA prompt this “tainted” DNA expulsion, potentially explaining a link to chronic inflammation associated with aging.
