Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation
Weiland, D. Brachvogel, B. Hornig-Do, H.-T. Neuhaus, J.F.G. Holzer, T. Tobin, Desmond J. Niessen, C.N. Wiesner, R.J. Baris, O.R.
Weiland, D.
Brachvogel, B.
Hornig-Do, H.-T.
Neuhaus, J.F.G.
Holzer, T.
Tobin, Desmond J.
Niessen, C.N.
Wiesner, R.J.
Baris, O.R.
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2018-01
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2017-08-16
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Abstract
Accumulation of large-scale mitochondrial DNA (mtDNA) deletions and chronic, subclinical inflammation are concomitant during skin aging, thus raising the question of a causal link. To approach this, we generated mice expressing a mutant mitochondrial helicase (K320E-TWINKLE) in the epidermis to accelerate the accumulation of mtDNA deletions in this skin compartment. Mice displayed low amounts of large-scale deletions and a dramatic depletion of mtDNA in the epidermis and showed macroscopic signs of severe skin inflammation. The mtDNA alterations led to an imbalanced stoichiometry of mitochondrial respiratory chain complexes, inducing a unique combination of cytokine expression, causing a severe inflammatory phenotype, with massive immune cell infiltrates already before birth. Altogether, these data unraveled a previously unknown link between an imbalanced stoichiometry of the mitochondrial respiratory chain complexes and skin inflammation and suggest that severe respiratory chain dysfunction, as observed in few cells leading to a mosaic in aged tissues, might be involved in the development of chronic subclinical inflammation.
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Weiland D, Brachvogel B, Hornig-Do H-T et al (2018) Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation. Journal of Investigative Dermatology. 138(1): 132-140.
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