Mitochondria in a "bottleneck"
Heteroplasmia, a phenomenon in which a cell contains both healthy mitochondria and organelles with damaged DNA, can cause more than two hundred mitochondrial diseases and contribute to the development of others, such as diabetes, cancer, Parkinson's and Alzheimer's diseases.
Defects in mtDNA primarily affect organs that require a lot of energy, including the heart, muscles and brain. Many mitochondrial diseases pose a danger not only to health, but also to life, and there are no ways to treat them.
The inner membrane of each mitochondria contains characteristic folds – crystals.
In normal mitochondria (left), these folds fill the entire interior space,
a violation of their structure leads to mitochondrial dysfunction (right).
Paternal mtDNA is not inherited, and all mitochondrial diseases are transmitted only through the maternal line. The number of mutations in the mtDNA of eggs increases with the age of women, but how much this affects the health of their children was not known until recently.
A multidisciplinary group of researchers led by Katerina D. Makova from the University of Pennsylvania took up the study of this issue. They took samples of blood and mucosal epithelial cells obtained by scraping from the inside of the cheeks from 39 healthy mother-child couples. The age of the mothers ranged from 25 to 59 years.
Sequencing confirmed an increase in the number of mutations in the mtDNA of eggs with age. A surprise was the greater number of such mutations in children born to older mothers.
The number of heteroplasmas in the mitochondria of the cells of the oral mucosa, leukocytes and in general
depending on the age of the mothers at the time of conception.
Graphic: Katerina Makova lab, Penn State University.
In addition, although it is already known that mitochondria in developing eggs pass through a "bottleneck" – a period in which the number of mtDNA molecules decreases, scientists did not know how much of a bottleneck it is. It turned out to be very narrow: the number of mitochondria decreases very significantly, which greatly increases the likelihood of mitochondrial diseases in children born as a result of fertilization of an egg with a large number of defective mitochondria slipping through the "bottleneck".
This is especially important for mothers with moderate or clinically non-manifested mitochondrial diseases. For the manifestation of many mitochondrial diseases, it is necessary that 70-80% of mtDNA carry mutations that disrupt the function of mitochondria, but for some of these diseases, depending on the localization and severity of mutations, only 10% of mutant mtDNA is sufficient.
This information may be useful when planning a family. If a preliminary study shows a high probability of having a child with mitochondrial diseases, doctors, when selecting embryos for in vitro fertilization, will be able to check them not only for the presence of chromosomal abnormalities and the most common (or available to parents) hereditary diseases, but also for the number of healthy mitochondria.
Article by Boris Rebolledo-Jaramillo et al. Maternal age effect and severe germ-line bottleneck in the inheritance of human mitochondrial DNA is published in open access in the electronic issue of the journal Proceedings of the National Academy of Sciences.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of The Pennsylvania State University:
Greater Rates of Mitochondrial Mutations Discovered in Children Born to Older Mothers.
15.10.2014