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

doi:10.3390/ijms22031006

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

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-mt^FVB, 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 language	English
Article number	1006
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	3
Pages (from-to)	1-23
Number of pages	23
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms22031006
Publication status	Published - 20.01.2021

Research Areas and Centers

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/ijms22031006

Cite this

Schilf, P., Künstner, A., Olbrich, M., Waschina, S., Fuchs, B., Galuska, C. E., Braun, A., Neuschütz, K., Seutter, M., Bieber, K., Hellberg, L., Sina, C., Laskay, T., Rupp, J., Ludwig, R. J., Zillikens, D., Busch, H., Sadik, C. D., Hirose, M., & Ibrahim, S. M. (2021). A mitochondrial polymorphism alters immune cell metabolism and protects mice from skin inflammation. International Journal of Molecular Sciences, 22(3), 1-23. Article 1006. https://doi.org/10.3390/ijms22031006

@article{08b629c8c55f49e6ac650cb41433203c,

title = "A mitochondrial polymorphism alters immune cell metabolism and protects mice from skin inflammation",

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.",

author = "Paul Schilf and Axel K{\"u}nstner and Michael Olbrich and Silvio Waschina and Beate Fuchs and Galuska, {Christina E.} and Anne Braun and Kerstin Neusch{\"u}tz and Malte Seutter and Katja Bieber and Lars Hellberg and Christian Sina and Tam{\'a}s Laskay and Jan Rupp and Ludwig, {Ralf J.} and Detlef Zillikens and Hauke Busch and Sadik, {Christian D.} and Misa Hirose and Ibrahim, {Saleh M.}",

year = "2021",

month = jan,

day = "20",

doi = "10.3390/ijms22031006",

language = "English",

volume = "22",

pages = "1--23",

journal = "International Journal of Molecular Sciences",

issn = "1661-6596",

publisher = "MDPI",

number = "3",

}

Schilf, P , Künstner, A, Olbrich, M, Waschina, S, Fuchs, B, Galuska, CE, Braun, A, Neuschütz, K, Seutter, M, Bieber, K, Hellberg, L, Sina, C , Laskay, T , Rupp, J , Ludwig, RJ, Zillikens, D, Busch, H , Sadik, CD , Hirose, M & Ibrahim, SM 2021, 'A mitochondrial polymorphism alters immune cell metabolism and protects mice from skin inflammation', International Journal of Molecular Sciences, vol. 22, no. 3, 1006, pp. 1-23. https://doi.org/10.3390/ijms22031006

TY - JOUR

T1 - A mitochondrial polymorphism alters immune cell metabolism and protects mice from skin inflammation

AU - Schilf, Paul

AU - Künstner, Axel

AU - Olbrich, Michael

AU - Waschina, Silvio

AU - Fuchs, Beate

AU - Galuska, Christina E.

AU - Braun, Anne

AU - Neuschütz, Kerstin

AU - Seutter, Malte

AU - Bieber, Katja

AU - Hellberg, Lars

AU - Sina, Christian

AU - Laskay, Tamás

AU - Rupp, Jan

AU - Ludwig, Ralf J.

AU - Zillikens, Detlef

AU - Busch, Hauke

AU - Sadik, Christian D.

AU - Hirose, Misa

AU - Ibrahim, Saleh M.

PY - 2021/1/20

Y1 - 2021/1/20

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85099695651&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/17f17b12-df34-3f58-924c-ffb590fd8406/

U2 - 10.3390/ijms22031006

DO - 10.3390/ijms22031006

M3 - Journal articles

C2 - 33498298

AN - SCOPUS:85099695651

SN - 1661-6596

VL - 22

SP - 1

EP - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 3

M1 - 1006

ER -

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

Abstract

Research Areas and Centers

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this