A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation
| Autor: | Tamás Laskay, Christian D. Sadik, Hauke Busch, Anne Braun, Christian Sina, Axel Künstner, Silvio Waschina, Saleh M. Ibrahim, Lars Hellberg, Paul Schilf, Katja Bieber, Kerstin Neuschütz, Ralf Ludwig, Malte Seutter, Detlef Zillikens, Jan Rupp, Michael Olbrich, Christina E. Galuska, Misa Hirose, Beate Fuchs |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
immunometabolism
Mitochondria Liver Mitochondrion Epidermolysis Bullosa Acquisita medicine.disease_cause lcsh:Chemistry Mice Lymphocytes lcsh:QH301-705.5 Spectroscopy Cells Cultured Mutation General Medicine Mitochondrial Proton-Translocating ATPases metabolomics Computer Science Applications Cell biology mitochondria MT-ATP8 conplastic mice Cytokines medicine.symptom mt-Atp8 Mitochondrial DNA Inflammation autoimmune disease Oxidative phosphorylation Biology DNA Mitochondrial Polymorphism Single Nucleotide Catalysis Article Inorganic Chemistry Immune system ATP8 mtDNA polymorphisms skin inflammation medicine Animals propionate Physical and Theoretical Chemistry Complex V Molecular Biology Gene Organic Chemistry Mice Inbred C57BL lcsh:Biology (General) lcsh:QD1-999 short chain fatty acids |
| Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 1006, p 1006 (2021) International Journal of Molecular Sciences Volume 22 Issue 3 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | Several genetic variants in the mitochondrial genome (mtDNA), including ancient polymorphisms, are associated with chronic inflammatory conditions, but investigating the functional consequences of such mtDNA polymorphisms in humans is challenging due to the influence of many other polymorphisms in both mtDNA and the nuclear genome (nDNA). Here, using the conplastic mouse strain B6-mtFVB, we show that in mice, a maternally inherited natural mutation (m.7778G > T) in the mitochondrially encoded gene ATP synthase 8 (mt-Atp8) of complex V impacts on the cellular metabolic profile and effector functions of CD4+ T cells and induces mild changes in oxidative phosphorylation (OXPHOS) complex activities. These changes culminated in significantly lower disease susceptibility in two models of inflammatory skin disease. Our findings provide experimental evidence that a natural variation in mtDNA influences chronic inflammatory conditions through alterations in cellular metabolism and the systemic metabolic profile without causing major dysfunction in the OXPHOS system. |
| Databáze: | OpenAIRE |
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