Mitochondria Are Sending Their DNA Into Our Brain Cells
Mitochondria have always seemed strange to us since they are direct descendants of ancient bacteria.
A recent study (link is external and opens in a new window) suggests that mitochondria may be even odder than previously assumed.
Mitochondria in our brain cells routinely toss their DNA into the nucleus, where it is integrated into the chromosomes. And these insertions could be causing harm. Among the study’s almost 1,200 participants, those who had more mitochondrial DNA insertions in their brain cells died sooner than those who had fewer insertions.
“We used to think that transferring DNA from mitochondria to the human genome was a rare occurrence,” says Martin Picard, a mitochondrial psychobiologist and associate professor of behavioral medicine at Columbia University’s Vagelos College of Physicians and Surgeons and the Robert N. Butler Columbia Aging Center. Picard co-led the study with Ryan Mills of the University of Michigan.
“It’s incredible that it appears to happen multiple 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.”
Mitochondrial DNA behaves as a virus
Mitochondria exist within all of our cells, but unlike other organelles, mitochondria have their own DNA, a tiny circular thread containing approximately three dozen genes. Mitochondrial DNA is a byproduct of the organelle’s forefathers, ancient germs that settled inside our single-celled ancestors some 1.5 billion years ago.
In recent decades, scientists discovered that mitochondrial DNA has occasionally “jumped” out of the organelle and into human chromosomes.
“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,” according to Mills.
The insertions, known as nuclear-mitochondrial segments (“pronounced new-mites”), have been accumulating 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,” Mills shares.
Mitochondrial DNA insertions are prevalent in the human brain.
Recent research has demonstrated that “NUMTogenesis” continues to occur now.
“Jumping mitochondrial DNA is not something that only happened in the distant past,” says Kalpita Karan, a postdoc in the Picard lab who co-led the study with Weichen Zhou, a Mills lab researcher. “It’s uncommon, but a new NUMT is integrated into the human genome about once in every 4,000 births.” This is one of the various ways mitochondria communicate with nuclear genes, which have been conserved from yeast to humans.”
Picard and Mills wondered if NUMTs may potentially originate in brain cells over our lifetimes after discovering that fresh inherited NUMTs are continually being formed.
“Inherited NUMTs are mostly benign, probably because they arise early in development and the harmful ones are weeded out,” according to Zhou. However, if a portion of mitochondrial DNA inserts itself into a gene or regulatory area, it could have serious ramifications for the individual’s health or lifespan. Neurons may be especially vulnerable to NUMT-caused damage since the brain does not generally produce a new brain cell to replace a damaged neuron.
To gain some insight, the researchers examined a population of human skin cells that can be cultivated and matured in a dish over several months, allowing for extraordinary longitudinal “lifespan” investigations.
These cultivated cells gradually acquired multiple NUMTs per month, and when the cells’ mitochondria were damaged by stress, they accumulated NUMTs four to five times faster.
“This shows a new way by which stress can affect the biology of our cells,” according to Karan. “Stress makes mitochondria more prone to leak bits of their DNA and these pieces can subsequently ‘infect’ the nuclear genome,” Zhou explains.” It is just one of the ways mitochondria influence our health in addition to energy generation.
“Mitochondria are cellular processors and a mighty signaling platform (link is external and opens in a new window),” Picard informs us. “We knew they could manipulate which genes are switched on and off. We now know that mitochondria can modify the nuclear DNA sequence itself.
