A Mitochondrial Polymorphism Alters Immune Cell Metabolism and Protects Mice from Skin Inflammation.
Int J Mol Sci
; 22(3)2021 Jan 20.
Article
em En
| MEDLINE
| ID: mdl-33498298
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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Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
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Linfócitos
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Epidermólise Bolhosa Adquirida
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Polimorfismo de Nucleotídeo Único
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article