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    Imbalance of Mitochondrial Respiratory Chain Complexes in the Epidermis Induces Severe Skin Inflammation

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    Publication date
    2018-01
    Author
    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.
    Keyword
    mtDNA; Mitochondrial DNA; RC; Respiratory chain; ROS; Reactive oxygen; Species
    Peer-Reviewed
    Yes
    
    Metadata
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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.
    URI
    http://hdl.handle.net/10454/15612
    Version
    No full-text in the repository
    Citation
    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 publisher’s version
    https://doi.org/10.1016/j.jid.2017.08.019
    Type
    Article
    Collections
    Life Sciences Publications

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