Why mtDNA (Mitochondrial DNA) is Maternally Inherited?

imhotep

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  • Mar 29, 2017
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    Mitochondrial DNA is the circular chromosome found inside the cellular organelles called mitochondria. Located in the cytoplasm, mitochondria are the site of the cell’s energy production and other metabolic functions. Offspring inherit mitochondria — and as a result mitochondrial DNA — from their mother. Thus, siblings from the same mother have the same mitochondrial DNA. In fact, any two people will have an identical mitochondrial DNA sequence if they are related by an unbroken maternal lineage. Because normally you get all of your mitochondria from your mother, they can be used to track your ancestry way, way, way back through your mother's lineage by looking at what's called your "mitochondrial haplogroup".

    In humans, mitochondrial DNA spans about 16,500 DNA base pairs, representing a small fraction of the total DNA in cells. Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function.
    Present in nearly all types of human cell, mitochondria are vital to our survival. They generate the majority of our adenosine triphosphate (ATP), the energy currency of the cell. So it's the main powerhouse but they are also involved in other tasks, such as signaling between cells and cell death, otherwise known as apoptosis.




    Why mtDNA is only passed down from the mother was always a question and previously it was believed that paternal mtDNA was eliminated soon after a sperm fuses with an oocyte, or developing egg, during fertilization, possibly through an immune-like search-and-destroy response.
    However, a recent study by a team of Researchers from the Oregon Health & Science University has found that while mature sperm do carry a small number of mitochondria, but they lack intact mtDNA.

    “We found that each sperm cell does bring 100 or so mitochondria as organelles when it fertilizes an egg, but there is no mtDNA in them,” says Shoukhrat Mitalipov, Ph.D., director of the Center for Embryonic Cell and Gene Therapy at OHSU, and Professor of Obstetrics and Gynecology, molecular and cellular biosciences, OHSU School of Medicine, OHSU Oregon National Primate Research Center.

    Researchers found that sperm cells are not only devoid of intact mtDNA, but they also lacked a protein essential for mtDNA maintenance, known as mitochondrial transcription factor A, or TFAM.
    Scientists aren’t sure why sperm are not allowed to contribute mtDNA, but Mitalipov theorizes that it may relate to the fact that a sperm uses a lot of mitochondrial energy in its biological impetus to fertilize an egg. It would thus accumulate mutations in mtDNA. The developing eggs known as oocytes, by contrast, draw energy primarily from surrounding cells, not from their own mitochondria, so maintain relatively pristine mtDNA.

    “Eggs pass on really good mtDNA at least partly because they don’t use mitochondria as a source of energy,” Mitalipov said.

    The 100 or so organelles in sperm are swamped by hundreds of thousands of mitochondria embedded in each egg cell — each carrying the 37 genes in mitochondrial DNA. The contribution of only maternal mtDNA is believed to confer an evolutionary advantage by limiting the risk of accumulations of mtDNA mutations that cause disease in offspring.

    Mitochondria control respiration and energy production within every cell of the body, so mutations in mtDNA can cause a range of potentially fatal disorders affecting organs with high-energy demands, such as the heart, muscle and brain.

    To help mothers prevent passing on known mtDNA disorders to their children, Mitalipov pioneered a method called Mitochondrial Replacement Therapy to replace mutant mtDNA through in vitro fertilization using healthy mtDNA from donor eggs.

    Congress has prevented the Food and Drug Administration from overseeing clinical trials using the procedure in the U.S., so clinical trials are instead being conducted overseas, including clinical trials in the United Kingdom to prevent disease and in Greece to treat infertility.

    Researchers write that the new discovery has important implications for human fertility and germ cell therapy.

    “Understanding the role of TFAM during sperm maturation and its function during fertilization may hold keys to our ability to treat certain infertility disorders and increase the efficiency of assisted reproductive technologies,” said corresponding author Dmitry Temiakov, Ph.D., a molecular biologist with Thomas Jefferson University in Philadelphia.