Three - parent fruit flies
The study of genes in fruit flies will help to find a cure for mitochondrial diseases
Having created "flies with three parents", scientists have identified a protein in them, with the help of which it is possible to get rid of the effects of mutations in mitochondrial genes. The discovery may give a hint on how to cope with human mitochondrial diseases using nuclear DNA, according to a press release from the University of Cambridge Gene discovery in fruit flies could help guide new treatments for mitochondrial disease.
Article by Chiang et al. A Genome-wide Screen Reveals that Reducing Mitochondrial DNA Polymerase Can Promote Elimination of Deleterious Mitochondrial Mutations is published in the journal Current Biology.
Mitochondria, the power plants of a cell, are structures that generate almost all the energy needed by cells for its vital activity. Mitochondria carry their own DNA – mitochondrial DNA, which encodes 13 proteins necessary for energy production. It is different from the DNA in the cell nucleus, which encodes the blueprint for the whole organism. While nuclear DNA is derived by half from each parent, mitochondrial DNA (mtDNA) is inherited exclusively from the mother.
A typical cell has two copies of nuclear DNA and hundreds or even thousands of copies of mtDNA. During the development and aging of the body, mtDNA continues to "renew" itself – and mutations may occur in some copies. This means that humans will carry a mixture of mutated and healthy mitochondrial genomes that are constantly competing with each other to take leading positions.
Some of these mutations are potentially harmful. In most cases, their number in the human body is insignificant. However, some people have a lot of them over time. When the proportion of harmful mutations exceeds 60-80% of all mtDNA copies in a cell, there is not enough energy to maintain normal cellular activity, and symptoms of the disease appear. These symptoms of the disease can be further transmitted to the next generation if mutated mitochondrial genomes are also present in large numbers in the mother's egg.
Scientists from the Gurdon Institute at the University of Cambridge have created a model for a fruit fly to investigate how the amount of mutated mtDNA changes over time and how a change in nuclear DNA will affect the development of mitochondrial disease. Researchers have created "three-parent flies" that inherit part of their mtDNA from a second mother. This is done under a microscope using tiny instruments, where mitochondria from the second mother are transferred into fertilized fly eggs carrying genetic information from their original mother and father. Flies carry two competing mitochondrial genomes, one healthy and one mutated, which are usually balanced and jointly transmitted to subsequent generations. However, a change in nuclear DNA can change the balance in favor of a single mitochondrial genome.
Using these three parent flies allowed scientists to measure the effect of each individual nuclear gene on competition between healthy and diseased mitochondrial genomes. They identified several nuclear DNA genes that could limit the transmission of the harmful mitochondrial genome during development or to the next generation. One of these genes encodes a protein called mtDNA polymerase. Reducing the amount of mtDNA polymerase increases the percentage of healthy mtDNA from 20% to 75% in just one generation. This eliminated the symptoms of the disease, and the new flies became much healthier.
A drawing from an article in Current Biology.
The results of the study show that reducing the activity of the gene in nuclear DNA can practically eliminate harmful mutations of mtDNA and can potentially be used to change the symptoms of mitochondrial disease. This could be a target for the development of drugs against mtDNA-related diseases.
Portal "Eternal youth" http://vechnayamolodost.ru