Title image: Mitochondria under the microscope.听
It鈥檚 one of the basic tenets of biology: We get our DNA from our mom and our dad.
But one notable exception has perplexed scientists for decades: Most animals, including humans, inherit the DNA inside their mitochondria鈥攖he cell鈥檚 energy centers鈥攆rom their mothers alone, with all traces of their father鈥檚 mitochondrial genome destroyed the moment sperm joins egg.
A new 抖阴旅行射 Boulder study sheds new light on why this happens, showing that when the process fails, and paternal mitochondria slips into a developing embryo, it can lead to lasting neurological, behavioral and reproductive problems in adults.
The study, conducted in roundworms, offers new clues about what may drive some mitochondrial disorders, which hinder the body鈥檚 ability to produce energy and collectively impact about one in 5,000 people. It also presents a novel approach for potentially preventing or treating them鈥攁 simple vitamin known as vitamin K2.
鈥淭hese findings provide important new insights into why paternal mitochondria must be swiftly removed during early development,鈥� said senior author Ding Xue, a professor in the Department of Molecular, Cellular and Developmental Biology (MCDB) at 抖阴旅行射听Boulder. 鈥淭hey also offer new hope for treatment of human diseases that may be caused when this process is compromised.鈥�
When cellular batteries run low
Often described as cellular batteries, mitochondria produce adenosine triphosphate (ATP), the energy that drives virtually all cell functions.
Mitochondria have their own distinct DNA, typically passed down exclusively from the mother.
In 2016, Xue published to spell out just how paternal mitochondria gets wiped out鈥攙ia a multi-faceted, self-destruct mechanism known as 鈥減aternal mitochondria elimination (PME),鈥� a process documented in worms, rodents and humans alike.
鈥淚t could be humiliating for a guy to hear, but it鈥檚 true,鈥� Xue joked. 鈥淥ur stuff is so undesirable that evolution has designed multiple mechanisms to make sure it is cleared during reproduction.鈥�
Some have theorized that after battling it out with millions of other sperm to penetrate an egg, sperm mitochondria are exhausted and genetically damaged in ways that would be evolutionarily disastrous if passed on to future generations.
Xue and his team set out to find out what happens when paternal mitochondria do not self-destruct.
They studied C. elegans, a translucent worm which contains only 1,000 cells but develops a nervous system, gut, muscles and other tissues similar to humans.
The team was unable to completely halt PME in the worms鈥攁 testament to how resilient this evolutionary process is. But they were able to delay it by about 10 hours. When they did so in fertilized eggs, it led to significant reductions in ATP. If the worms survived at all, they had impaired cognition, altered activity and difficulty reproducing.
When the researchers treated the worms with a form of vitamin K2 known as MK-4 (best known as a bone health supplement) it restored ATP levels to normal in the embryos and improved memory, activity and reproduction in the adult worms.
Hope for hard-to-treat diseases
Ding Xue
The authors note that there are only a few documented cases in which paternal mitochondrial DNA might have been found in human adults. 28-year-old man had trouble breathing, weak muscles and could not tolerate exercise. describes 17 members of three unrelated multi-generational families who had fatigue, muscle pain, speech delays and neurological symptoms.
More research is needed in larger animals, but Xue suspects that in some cases, as with the worms, a mere delay in PME could be fueling hard-to-diagnose human diseases.
鈥淚f you have a problem with ATP it can impact every stage of the human life cycle,鈥� he said.
Xue imagines a day when some families with a history of mitochondrial disorders take vitamin K2 prenatally as a precautionary measure. The study, and the lab鈥檚 ongoing research, could also lead to new ways to diagnose or treat such disorders.
鈥淭here are a lot of diseases that are poorly understood. No one really knows what is going on. This research offers clues,鈥� Xue said.
