A mitochondrial polymorphism alters immune cell metabolism and protects mice from skin inflammation

Paul Schilf, Axel Künstner, Michael Olbrich, Silvio Waschina, Beate Fuchs, Christina E. Galuska, Anne Braun, Kerstin Neuschütz, Malte Seutter, Katja Bieber, Lars Hellberg, Christian Sina, Tamás Laskay, Jan Rupp, Ralf J. Ludwig, Detlef Zillikens, Hauke Busch, Christian D. Sadik, Misa Hirose*, Saleh M. Ibrahim

*Corresponding author for this work


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.

Original languageEnglish
Article number1006
JournalInternational Journal of Molecular Sciences
Issue number3
Pages (from-to)1-23
Number of pages23
Publication statusPublished - 20.01.2021

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)


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