The study, titled “Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts,” appears in PLOS Biology.
Mitochondria in our brain cells frequently fling their DNA into the nucleus, the study found, where the DNA becomes integrated into the cells’ chromosomes.
And these insertions may be causing harm: Among the study’s nearly 1,200 participants, those with more mitochondrial DNA insertions in their brain cells were more likely to die earlier than those with fewer insertions.
Mitochondrial DNA behaves like a virus Mitochondria live inside all our cells, but unlike other organelles, mitochondria have their own DNA, a small circular strand with about three dozen genes.
Mitochondrial DNA is a remnant from the organelle’s forebears: ancient bacteria that settled inside our single-celled ancestors about 1.5 billion years ago.
Mitochondrial DNA insertions are common in the human brain Research in just the past few years has shown that “NUMTogenesis” is still happening today.
Their analysis showed that nuclear mitochondrial DNA insertion happens in the human brain—mostly in the prefrontal cortex—and likely several times over during a person’s lifespan.
These cultured cells gradually accumulated several NUMTs per month, and when the cells’ mitochondria were dysfunctional from stress, the cells accumulated NUMTs four to five times more rapidly.
Mitochondria have always seemed a little strange, being the direct offspring of ancient bacteria. A recent study suggests that mitochondria may be even stranger than previously believed.
The paper, published in PLOS Biology, is titled “Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts.”.
The study discovered that our brain cells’ mitochondria regularly launch their DNA into the nucleus, where it is incorporated into the chromosomes of the cells. Moreover, there may be negative effects from these insertions: of the approximately 1,200 participants in the study, those who had more mitochondrial DNA insertions in their brain cells had an increased risk of dying before their time.
The transfer of DNA from mitochondria to the human genome was once thought to be an uncommon occurrence, according to Martin Picard, an associate professor of behavioral medicine at Columbia University’s Vagelos College of Physicians and Surgeons and the Robert N. Butler Columbia Aging Center. Along with Ryan Mills from the University of Michigan, Picard led the research.
Picard continues, “I find it astounding that it seems to be occurring multiple times in a person’s life.”. “We discovered numerous instances of these insertions in various brain regions, but not in blood cells, which clarifies why this phenomenon was overlooked by numerous prior studies that examined blood DNA. “. .
Mitotic DNA exhibits viral characteristics.
In contrast to other organelles, mitochondria possess a small circular strand containing roughly thirty genes. Mitochondria are found inside all of our cells. A trace of the ancient bacteria that once inhabited our single-celled ancestors approximately 1.5 billion years ago is mitochondrial DNA.
Over the last few decades, scientists have found that human chromosomes have occasionally experienced mitochondrial DNA “jumping” out of the organelle.
According to Mills, “the mitochondrial DNA behaves like a virus in that it uses cuts in the genome and pastes itself in, or like jumping genes known as retrotransposons that move around the human genome.”.
The insertions, known as nuclear-mitochondrial segments, or NUMTs (pronounced “new-mites”), have been building up in our chromosomes for millions of years.
Because of this, each of us has hundreds of chromosomes that contain largely benign mitochondrial DNA segments that we inherited from our ancestors and carry with us today, according to Mills.
Human brains often contain mitochondrial DNA insertions.
Studies conducted in the last few years have demonstrated that “NUMTogenesis” continues to occur.
Weichen Zhou, a research investigator in the Mills lab, and Kalpita Karan, a postdoc in the Picard lab, conducted the research. “Jumping mitochondrial DNA is not something that only happened in the distant past,” says Karan. Roughly one new NUMT integrates into the human genome for every 4,000 births, though this is an uncommon occurrence. This is just one method that mitochondria communicate with nuclear genes, a process that has been carried over from yeast to humans. “. .
Thoughts of whether NUMTs could also develop in brain cells during our lifespan occurred to Picard and Mills upon realizing that new inherited NUMTs are still being created.
According to Zhou, “inherited NUMTs are mostly benign, probably because the harmful ones are weeded out and they arise early in development.”. However, the health and lifespan of that individual may be significantly impacted if a fragment of mitochondrial DNA inserts itself within a gene or regulatory area. Since the brain rarely produces new brain cells to replace damaged neurons, it is possible that neurons are especially vulnerable to damage from NUMTs.
In order to investigate the scope and effects of novel NUMTs in the brain, the researchers collaborated with Hans Klein, an assistant professor at Columbia University’s Center for Translational and Computational Neuroimmunology, who provided DNA sequences from study participants in the ROSMAP aging project, which is directed by Rush University’s David Bennett). Using banked tissue samples from over one thousand senior citizens, the researchers searched for NUMTs in various brain regions.
Their investigation revealed that nuclear mitochondrial DNA insertion occurs in the human brain, primarily in the prefrontal cortex, and probably occurs multiple times over the course of a lifetime.
Additionally, they discovered that those with a higher number of NUMTs in their prefrontal cortex passed away sooner than those with a lower number. “This indicates that NUMTs may have functional implications and potentially impact lifespan for the first time,” says Picard. “NUMT accumulation is another mechanism of genome instability that may be involved in lifespan, functional decline, and aging. “.”.
The generation of NUMTogenesis is accelerated by stress.
What is the brain’s cause of NUMTs, and why do some areas accumulate more than others?
A population of human skin cells that can be aged and cultured in a dish over several months, allowing for exceptional longitudinal “lifespan” studies, was examined by the researchers in order to obtain some clues.
The cultivated cells progressively accumulated multiple NUMTs monthly; in instances where the cells’ mitochondria were impaired due to stress, the rate of NUMT accumulation increased four to five times.
The way that stress can impact our cells’ biology is demonstrated by this, according to Karan. According to Zhou, “stress increases the likelihood that mitochondria will leak bits of their DNA, which can then ‘infect’ the nuclear genome.”. It’s just one way mitochondria influence our health in addition to supplying energy.
