A Keratin Scaffold Regulates Epidermal Barrier Formation, Mitochondrial Lipid Composition, And Activity

    December 2015 in “ The Journal of Cell Biology
    Vinod Kumar, Jamal-Eddine Bouameur, Janina Bär, Robert H. Rice, Hue‐Tran Hornig‐Do, Dennis R. Roop, Nicole Schwarz, Susanne Brodesser, Sören Thiering, Rudolf E. Leube, Rudolf J. Wiesner, Preethi Vijayaraj, Christina B. Brazel, Sandra Heller, Hans Binder, Henry Loeffler‐Wirth, Peter Seibel, Thomas M. Magin
    TLDR Keratin is crucial for skin barrier formation and affects mitochondrial function.
    The study investigated the role of keratin intermediate filaments (KIFs) in epidermal barrier formation, mitochondrial lipid composition, and activity. Mice lacking type I or type II keratins exhibited severe barrier defects and fragile skin, resulting in perinatal mortality. Comparative proteomics revealed dysregulation of cornified envelope constituents, including downregulation of desmoglein 1, despite the persistence of loricrin expression and upregulation of Nrf2 targets. The findings highlighted keratins as essential scaffolds for cornified envelope formation and demonstrated that KIFs intrinsically regulate mitochondrial lipid composition and activity. This research provided insights into the complexity of keratinopathies and their association with barrier disorders.
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