Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation
Publication date
2018-01Author
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.
Peer-Reviewed
Yes
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Show full item recordAbstract
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.Version
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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.Link to Version of Record
https://doi.org/10.1016/j.jid.2017.08.019Type
Articleae974a485f413a2113503eed53cd6c53
https://doi.org/10.1016/j.jid.2017.08.019