According to the study, mitochondria in our brain cells are flinging their DNA into the nucleus quite frequently. Within those cells, that DNA gets inserted into the cell’s chromosomes. And these insertions may well be doing damage: Among almost 1,200 participants, results showed that more mitochondrial DNA insertions in the brain cells correlated with an increased risk of earlier death.
We used to think that the transfer of DNA from mitochondria to the human genome was a rare occurrence,
It’s stunning that it appears to be happening several times during a person’s lifetime, Picard adds,
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.
Martin Picard
Mitochondria live in all our cells, but unlike other organelles, mitochondria sport their own DNA—a small, circular strand with about three dozen genes. Mitochondrial DNA is a relic from the organelle’s forebears, ancient bacteria that settled inside our single-celled ancestors about 1.5 billion years ago.
It has been two decades since scientists found out that mitochondrial DNA “jumped” into the human chromosomes from these cellular organelles.
The mitochondrial DNA behaves similar to a virus in that it makes use of cuts in the genome and pastes itself in, or like jumping genes known as retrotransposons that move around the human genome.
Ryan Mills
These insertions are called nuclear-mitochondrial segments (NUMTs, pronounced “new-mites”), and they have been piling up in our chromosomes for millions of years.
As a result, all of us are walking around with hundreds of vestigial, mostly benign, mitochondrial DNA segments in our chromosomes that we inherited from our ancestors.
Ryan Mills
Insertions of mitochondrial DNA are commonly observed in the human brain
Even recently, research in just the past few years has demonstrated that “NUMTogenesis” is still occurring.
Jumping mitochondrial DNA is not something that only happened in the distant past,
It’s rare, but a new NUMT becomes integrated into the human genome about once in every 4,000 births. This is one of many ways, conserved from yeast to humans, by which mitochondria talk to nuclear genes.
Kalpita Karan
This led Picard and Mills to the question: Could NUMTs also form in our brain cells during our lifetime?
Inherited NUMTs are mostly benign, probably because they arise early in development and the harmful ones are weeded out.
Weichen Zhou
But if a fragment of mitochondrial DNA inserts itself within a gene or regulatory region, it might have important consequences for health or longevity. Neurons may be more susceptible to the damage caused by NUMTs since when a neuron is damaged, the brain usually does not make a new brain cell to take its place.
The team collaborated with Hans Klein, an assistant professor in the Center for Translational and Computational Neuroimmunology at Columbia, who had access to DNA sequences from participants in the ROSMAP study of aging, led by David Bennett at Rush University, to investigate how many new NUMTs are really in the brain and the effect of having those NUMTs. They looked for NUMTs throughout the brain, using banked tissue samples from more than 1,000 older adults, in searches that turned up a wide range.
Their results revealed nuclear mitochondrial DNA insertion in the human brain does take place majorly in the prefrontal cortex through at least one but probably several times in most people’s lives.
They also noted that people with a greater number of NUMTs in the prefrontal cortex died younger than those with fewer NUMTs.
NUMT accumulation can be added to the list of genome instability mechanisms that may contribute to aging, functional decline, and lifespan.
Martin Picard
What can cause NUMTs in the brain, and why do some regions accumulate more than others?
Looking for some clues, the researchers examined a population of human skin cells that can be cultured and aged in a dish over months, enabling exceptional longitudinal “lifespan” studies.
These cultured cells gradually accumulated a few NUMTs per month, and when stressed, the cells’ mitochondria were dysfunctional and their NUMTs accumulated four to five times faster.
Also, Read| Researchers discovered a new code supporting the gene activity
This shows a new way by which stress can affect the biology of our cells,
Stress makes mitochondria more likely to release pieces of their DNA and these pieces can then ‘infect’ the nuclear genome,
We knew they can control which genes are turned on or off. Now we know mitochondria can even change the nuclear DNA sequence itself.
Weichen Zhou
Source: CUMIC Columbia News
Journal Reference: Weichen Zhou, Kalpita R. Karan, Wenjin Gu, Hans-Ulrich Klein, Gabriel Sturm, Philip L. De Jager, David A. Bennett, Michio Hirano, Martin Picard, Ryan E. Mills. Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts. PLOS Biology, 2024; 22 (8): e3002723 DOI: https://doi.org/10.1371/journal.pbio.3002723.
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