Mitochondria.Credits: Wikipedia Commons
One of the first population-scale studies on how common genetic traits are affected by changes in mitochondrial DNA, the driving force of human cells, was the European Molecular Biology Laboratory at the Wellcome Trust Sanger Institute, University of Cambridge, EMBL. Tokoro (EMBL-EBI) and its collaborators. The team identified the association of mtDNA variants with amino acids, N-formylmethionine (fMet), and the impact of fMet on the risk of developing a variety of common late-onset diseases.
Study published today Nature medicine Higher fMet levels were found to be associated with a wide range of late-onset diseases and an increased risk of death from all causes, the potential of fMet as a biomarker of aging and disease risk, and mitochondrial DNA variants. Shows the importance of research in.
Mitochondria are organelles found in the cells of all complex organisms. They perform many important biological functions, including the production of about 90 percent of the energy that cells need to function. Mitochondria are unique in that they have their own genetic code known as mitochondrial DNA (mtDNA). This is different from the DNA contained in the nucleus of every cell in the body of an organism1. mtDNA is passed down from mother to child.
Many common diseases are affected by mitochondrial damage or destruction, including hereditary diseases such as diabetes, heart disease, and depression that are affected by mutations in mtDNA.
Over time, the accumulation of mtDNA mutations leads to different strains of the population known as haplogroups that give specific properties. Previous studies have shown that the haplogroup Uk, found in 10% of the European population, prevents diseases such as Parkinson’s disease and ischemic stroke (IS).
In this study, we analyzed two large datasets, including genetic variation of mtDNA and blood cell count. Plasma proteinTo understand the molecular mechanisms behind the association between mtDNA and disease.
In the INTERVAL dataset of up to 16,000 participants, researchers identified a significant association between the levels of fMet and mtDNA variants in the haplogroups Uk and H32. The team then used a cellular model to validate these associations. A cohort of patients with ischemic stroke measured fMet levels and found that they had lower fMet levels compared to healthy controls.
Next, researchers analyzed data from EPIC-Norfolk, a 20-year follow-up study of participants’ health status, to see if differences in fMet between individuals are associated with a wider range of late-onset illnesses. Asked. In contrast to ischemic stroke, higher fMet levels were associated with an increased risk of illnesses such as kidney disease and heart failure.
“We knew that the UK haplogroup would provide some protection against ischemic stroke and Parkinson’s disease. Our findings upregulate N-formylmethionine (fMet). It suggests that variants of mitochondrial DNA may be involved in this protection. Surprisingly, these same variants are also associated with a higher risk of other diseases. Molecular mechanism When there is a need at work, fMet seems to be a promising biomarker that individuals can use to more accurately predict their risk of developing a wide range of illnesses. Common illness“Dr. Nachai, lead author of the Wellcome Trust Sanger Institute and EMBL’s European Bioinformatics Institute (EMBL-EBI) research.
“When we examined molecular processes using a human cell model, mutants of the haplogroup Uk regulated protein synthesis and degradation in both mitochondria and cytoplasm, affecting cellular processes beyond mitochondrial bioenergy. I found out to give. Ischemic stroke (IS), our findings suggest that some of the protective effects of the mtDNA haplogroup Uk may be due to reduced protein clearance mediated by fMet, “said the University of Cambridge. Professor Patrick Chinnery, senior author of the study, said.
“Our findings reveal that mtDNA mutants play an important role in some pathologies and play a deeper role in cell homeostasis than previously thought. mtDNA needs to be carefully considered when investigating the diagnosis and providing treatment for age. Related disorders, “said Dr. Aurora Gomez Duran, lead author of the University of Cambridge study.
Only about 6,000 individuals evaluate about 1,000 molecular traits in this study, and other important associations between mtDNA variants and genetic traits remain hidden so far. The next step is to scale up this study to identify other properties associated with mtDNA mutants.
“Our research is about health disease.. N-formylmethionine (fMet) is a promising biomarker that may one day help individuals monitor. Disease risk Plan preemptive intervention. This study was a true collaboration that combined data from genome-wide association studies, cell lines, and computational analyses to provide rich insights into human biology, “said the Welcome Sanger Institute’s senior research. The author, Professor Nicole Solanzo, said.
Na Cai et al, a mitochondrial DNA variant, regulates the risk of N-formylmethionine, protein homeostasis, and late-onset human disease. Nature medicine (2021). DOI: 10.1038 / s41591-021-01441-3
Provided by
Wellcome Trust Sanger Institute
Quote: The association between amino acids and various common diseases is personally obtained from medicalxpress.com/news/2021-08-link-amino-acid-range-common on August 24, 2021. May help predict risk (August 24, 2021) .html
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The association of amino acids with various common illnesses can help predict an individual’s risk
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