Scientists have been curious about why animals inherit mitochondrial DNA—the genetic material in a cell’s powerhouses—exclusively from their mothers. New findings shed light on this phenomenon and suggest potential treatments for mitochondrial conditions.
We typically receive our genetic material from both our mother and father.
However, there is a significant exception that has puzzled researchers for many years: The majority of animals, including humans, get their mitochondrial DNA solely from their mothers. The father’s mitochondrial DNA is destroyed the instant the sperm fertilizes the egg.
A recent study from the University of Colorado Boulder, published on October 4 in the journal Science Advances, explores the reasons behind this occurrence. It reveals that if paternal mitochondria enter the developing embryo, it could lead to serious neurological, behavioral, and reproductive issues later in life.
This research, conducted on roundworms, provides new insights into some mitochondrial disorders, which impair the body’s energy production and affect roughly one in 5,000 people. Additionally, it suggests a potential remedy: a vitamin known as Vitamin K2.
“Our findings offer valuable information regarding why paternal mitochondria need to be quickly eliminated during early development,” stated senior author Ding Xue, a professor at the Department of Molecular, Cellular and Developmental Biology (MCDB) at the University of Colorado Boulder. “They also present new possibilities for treating human diseases linked to this process failing.”
When Energy Sources Dwindle
Mitochondria, often referred to as the cell’s batteries, generate adenosine triphosphate (ATP), the energy necessary for nearly all cellular functions.
These organelles contain unique DNA that is usually inherited from the mother alone.
In 2016, Xue published one of the first studies detailing how paternal mitochondria are eliminated through a complex self-destruction process termed “paternal mitochondria elimination (PME),” which has been observed in worms, rodents, and humans.
“It might be a bit embarrassing for men, but it’s true,” Xue quipped. “Our contributions are so undesirable that evolution has adapted several mechanisms to ensure they are removed during reproduction.”
Some researchers propose that the mitochondria in sperm are worn out and genetically compromised after competing with countless others to fertilize the egg, making their survival in future generations potentially harmful.
Xue and his team aimed to investigate the effects when paternal mitochondria do not undergo self-destruction.
They examined C. elegans, a transparent worm with only 1,000 cells, yet it develops a nervous system, digestive system, muscles, and other tissues akin to those found in humans.
While the team couldn’t completely stop PME in the worms—highlighting how robust this evolutionary mechanism is—they managed to delay it by about 10 hours. This delay in fertilized eggs resulted in a significant drop in ATP production. Surviving worms displayed impaired cognitive function, altered behaviors, and reproductive challenges.
When the researchers administered a form of vitamin K2, specifically MK-4 (widely recognized as a supplement for bone health), it normalized ATP levels in the embryos and enhanced memory, activity, and reproductive health in the adult worms.
Potential for Understanding Little-Known Diseases
The authors mention only a handful of documented instances of paternal mitochondrial DNA in humans. One study details a 28-year-old man experiencing respiratory issues, muscle weakness, and exercise intolerance. Another describes 17 individuals from three unrelated multi-generational families suffering from fatigue, muscle pain, speech delays, and neurological symptoms.
Further investigation is necessary in larger animals, but Xue suspects that, similar to the worms, merely delaying PME might be a factor in some challenging-to-diagnose human diseases.
“A deficiency in ATP can affect all stages of human life,” he explained.
Xue envisions a future where families with a history of mitochondrial disorders could take Vitamin K2 as a preventative measure during pregnancy. The findings from this study, along with ongoing research, could lead to improved methods for diagnosing and treating mitochondrial disorders.
“There are numerous diseases that remain poorly understood. The exact mechanisms are unclear. This research provides valuable hints,” Xue concluded.
