Broader Implications for Aging and Disease: The integration of mitochondrial DNA into nuclear DNA is not a new phenomenon; it has been occurring for millions of years. However, the active creation of these insertions in modern humans, particularly in brain cells, raises concerns about their impact on cognitive functions and overall neurological health. The findings suggest that these insertions could be linked to various age-related diseases and could provide new avenues for understanding the biological mechanisms of aging ScienceDaily andEurekAlert!
Recent research has uncovered a surprising mechanism by which mitochondria—the energy-producing organelles in cells—may influence health and lifespan beyond their traditional role. A study published in PLOS Biology reveals that mitochondrial DNA (mtDNA) frequently inserts itself into the nuclear DNA of brain cells, a process that may be linked to shorter lifespans.
Mitochondria, which are believed to be descendants of ancient bacteria, possess their own DNA, separate from the nuclear DNA found in the cell’s nucleus. The study led by Martin Picard, an associate professor at Columbia University, and Ryan Mills from the University of Michigan, found that these mitochondrial DNA segments often move into the cell’s nucleus and integrate with its chromosomes. This phenomenon, known as “NUMTogenesis,” was previously thought to be rare, but the new findings suggest it may occur multiple times throughout a person’s life.
A surprise finding on the prevalence of mitochondrial DNA transfer to nucleus of brain cells (to form Numt, “numtogenesis”) with evidence of adverse outcomes in a cohort of ~1,200 individualshttps://t.co/RccF4s6Uzv @PLOSBiology @ryan_e_mills @umichmedicine pic.twitter.com/brRc4jJs87
— Eric Topol (@EricTopol) August 22, 2024
The research, which involved analyzing DNA from nearly 1,200 participants, showed that individuals with more mitochondrial DNA insertions in their brain cells, particularly in the prefrontal cortex, tended to die earlier than those with fewer insertions. “This suggests for the first time that NUMTs may have functional consequences and possibly influence lifespan,” Picard noted. The presence of these insertions adds to the understanding of genome instability mechanisms that contribute to aging and functional decline.
Mitochondrial DNA insertions, known as NUMTs (nuclear mitochondrial segments), have been present in human chromosomes for millions of years, accumulating like vestigial remnants. However, this study reveals that NUMTs are not just ancient artifacts; they continue to form and integrate into our DNA today. Unlike inherited NUMTs, which generally appear early in development and tend to be benign, these newly formed insertions in the brain could potentially cause harm, especially if they insert themselves within important genes or regulatory regions.
Further exploration into why some brain regions, like the prefrontal cortex, accumulate more NUMTs than others led researchers to investigate the impact of stress on mitochondrial function. In a series of experiments with cultured human skin cells, researchers discovered that when cells experienced mitochondrial stress, they accumulated NUMTs at a rate four to five times faster than under normal conditions. This finding suggests that stress could accelerate the release of mitochondrial DNA into the nucleus, thereby affecting cellular health and longevity.
“Stress makes mitochondria more likely to release pieces of their DNA, and these pieces can then ‘infect’ the nuclear genome,” explained Weichen Zhou, a researcher involved in the study. This discovery indicates that mitochondrial DNA can behave much like a virus, exploiting cuts in the genome to insert itself, similar to the behavior of retrotransposons—jumping genes that move around the human genome.
This research highlights a new dimension in how mitochondria affect our health beyond their traditional role in energy production. “Mitochondria are cellular processors and a mighty signaling platform,” Picard said. “We knew they could control which genes are turned on or off. Now we know mitochondria can even change the nuclear DNA sequence itself.”
These DNA insertions may be linked to early death
A new study finds that mitochondria in our brain cells frequently fling their DNA into the cells’ nucleus, where the mitochondrial DNA integrates into chromosomes, possibly causing harm.https://t.co/14RjmEbnYY
— Shahriyar Gourgi (@ShahriyarGourgi) August 23, 2024
The study provides a new understanding of the dynamic interaction between mitochondria and nuclear DNA, suggesting that mitochondria play a more complex role in human biology than previously thought. It also opens up new avenues for research into how stress and mitochondrial dysfunction might contribute to aging and age-related diseases.
The research was supported by grants from the U.S. National Institutes of Health, the Baszucki Brain Research Fund, and the University of Michigan Alzheimer’s Disease Center Berger Endowment.
More information
- Potential Therapeutic Advances: Understanding how NUMTs contribute to disease processes could lead to new diagnostic markers or therapeutic targets. For instance, monitoring the presence and frequency of NUMTs in brain cells might help identify individuals at higher risk for certain neurological conditions. Strategies to minimize or repair harmful mitochondrial DNA integration could provide new treatments for age-related diseases Earth.com
- Martin Picard, Columbia University: “It’s stunning that it appears to be happening several times during a person’s lifetime. We found lots of these insertions across different brain regions, but not in blood cells, explaining why dozens of earlier studies analyzing blood DNA missed this phenomenon.” Picard emphasizes the unexpected frequency and potential impact of these insertions on health and lifespan CUIMC
- Weichen Zhou, University of Michigan: “Stress makes mitochondria more likely to release pieces of their DNA, and these pieces can then ‘infect’ the nuclear genome,” highlighting the role of stress in accelerating the aging process through mitochondrial DNA dynamics Earth.com
Key Points:
i. A study published in PLOS Biology found that mitochondrial DNA frequently inserts itself into the nuclear DNA of brain cells, potentially impacting lifespan.
ii. These insertions, known as NUMTs (nuclear mitochondrial segments), were more prevalent in individuals with shorter lifespans, suggesting a link between NUMTs and early death.
iii. The research revealed that mitochondrial DNA behaves like a virus, inserting itself into the nuclear genome, a process accelerated by cellular stress.
iv. Stress on mitochondria can increase the rate of NUMT accumulation, further suggesting that stress impacts cellular health beyond its immediate effects.
v. The findings highlight a new role for mitochondria in influencing human health and aging, expanding beyond their traditional function in energy production.
Kirk Volo – Reprinted with permission of Whatfinger News