Research uncovers disease-aggravating mutation in mouse model of GRACILE syndrome

Research uncovers disease-aggravating mutation in mouse model of GRACILE syndrome

Iron overload, variant gene and malaria resistance linked in African study The work, carried out at the Folkhälsan Research Center and the University of Helsinki, revealed that, due to an extremely unlikely coincidence, a random mutation in the mt-Cyb gene had appeared, affecting exactly the same part of mitochondria as the GRACILE mutation and worsening the disease of the mice. According to computer simulations and spectroscopic measurements performed by collaborators in Finland and Poland, the amino acid change identified in the mice slows down the movement of a part of Rieske protein needed in electron transfer during cellular respiration. The researchers say that this is the first time such an interaction between the nuclear and mitochondrial genomes has been delineated down to almost atomic level. Docent Jukka Kallijärvi tells that the discovery is an extreme example of an unexpectedly large effect of the genetic background on the course of an inherited disease. Modifying the nuclear genome has been commonplace in experimental animal models for a long time, but we are yet to develop a technique with which to transfer mutations in a targeted manner to as many as thousands of copies of the mitochondrial genome in every cell. Our unique mouse model, which carries the spontaneous mtDNA variant, could prove a valuable tool in studies of both mitochondrial diseases and the function of mitochondria in general." Docent Jukka Kallijärvi The otherwise wild-type mice carrying the newly discovered variant appear healthy, but their metabolism is not entirely normal. An equivalent mutation is found naturally in the three-toed sloth species of South America, an animal with an extremely slow metabolism and an energy-poor diet. "It is interesting to speculate that the mtDNA variant may be beneficial in certain conditions, which is why it occurs in nature. In further studies, we are interested in the effect of this variant, which subtly affects mitochondrial functions, on metabolism and aging in mice", Kallijärvi says. Source: University of Helsinki Journal reference: Purhonen, J., et al. (2020) A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice. Nature Communications . doi.org/10.1038/s41467-019-14201-2 .



Also in Industry News

How to decide whether or not to start treatment for prostate cancer?
How to decide whether or not to start treatment for prostate cancer?

0 Comments

How to decide whether or not to start treatment for prostate cancer?

Read More

Analysis of the SARS-CoV-2 proteome via visual tools
Analysis of the SARS-CoV-2 proteome via visual tools

0 Comments

Analysis of the SARS-CoV-2 proteome via visual tools

Read More

$65m investment increases British Patient Capital’s exposure to life sciences and health technology
$65m investment increases British Patient Capital’s exposure to life sciences and health technology

0 Comments

$65m investment increases British Patient Capital’s exposure to life sciences and health technology

Read More