关键词： ATP8 autoimmune disease complex V conplastic mice immunometabolism metabolomics mitochondria mt-Atp8 mtDNA polymorphisms propionate short chain fatty acids skin inflammation

Mesh ： Animals Cells, Cultured Cytokines / metabolism DNA, Mitochondrial / genetics Epidermolysis Bullosa Acquisita / genetics metabolism Lymphocytes / metabolism Mice Mice, Inbred C57BL Mitochondria, Liver / genetics metabolism Mitochondrial Proton-Translocating ATPases / genetics Polymorphism, Single Nucleotide

来  源：   DOI：10.3390/ijms22031006   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
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