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dc.contributor.authorWeiland, D.*
dc.contributor.authorBrachvogel, B.*
dc.contributor.authorHornig-Do, H.-T.*
dc.contributor.authorNeuhaus, J.F.G.*
dc.contributor.authorHolzer, T.*
dc.contributor.authorTobin, Desmond J.*
dc.contributor.authorNiessen, C.N.*
dc.contributor.authorWiesner, R.J.*
dc.contributor.authorBaris, O.R.*
dc.date.accessioned2018-04-23T15:13:35Z
dc.date.available2018-04-23T15:13:35Z
dc.date.issued2018-01
dc.identifier.citationWeiland 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.en_US
dc.identifier.urihttp://hdl.handle.net/10454/15612
dc.descriptionNoen_US
dc.description.abstractAccumulation 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.en_US
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (Wi 889/6-3 to RJW, SFB 829 A14 to RJW, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases–CECAD to RJW, BR2304/9-1 to BB, and SFB 829 A1, A5, and Z2 to CMN) and the Center of Molecular Medicine Cologne of the Medical Faculty (CMMC, to RJW)en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1016/j.jid.2017.08.019en_US
dc.subjectmtDNA; Mitochondrial DNA; RC; Respiratory chain; ROS; Reactive oxygen; Speciesen_US
dc.titleImbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammationen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-08-16
dc.date.application2017-09-01
dc.typeArticleen_US
dc.type.versionNo full-text in the repositoryen_US


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