2. Academic Validation
  3. A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity

  • J Cell Biol. 2015 Dec 7;211(5):1057-75. doi: 10.1083/jcb.201404147.
Vinod Kumar 1,  Jamal-Eddine Bouameur 1,  Janina Bär 1,  Robert H Rice 2,  Hue-Tran Hornig-Do 3,  Dennis R Roop 4,  Nicole Schwarz 5,  Susanne Brodesser 6,  Sören Thiering 1,  Rudolf E Leube 5,  Rudolf J Wiesner 6,  Preethi Vijayaraj,  Christina B Brazel 1,  Sandra Heller 7,  Hans Binder 8,  Henry Löffler-Wirth 8,  Peter Seibel 7,  Thomas M Magin 9
Affiliations

Affiliations

  • 1 Translational Centre for Regenerative Medicine Leipzig, University of Leipzig, 04103 Leipzig, Germany Institute of Biology, Division of Cell and Developmental Biology, University of Leipzig, 04103 Leipzig, Germany.
  • 2 Department of Environmental Toxicology, University of California, Davis, Davis, CA 95616.
  • 3 Center for Physiology and Pathophysiology, Institute for Vegetative Physiology, University of Cologne, 50931 Cologne, Germany.
  • 4 Department of Dermatology, University of Colorado, Denver, CO 80045 Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology, University of Colorado, Denver, CO 80045.
  • 5 Institute of Molecular and Cellular Anatomy, Rheinisch-Westfälische Technische Hochschule Aachen University, 52074 Aachen, Germany.
  • 6 Center for Physiology and Pathophysiology, Institute for Vegetative Physiology, University of Cologne, 50931 Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Medical Faculty, University of Cologne, 50931 Cologne, Germany Center for Molecular Medicine Cologne, 50931 Cologne, Germany.
  • 7 Center for Biotechnology and Biomedicine, 04103 Leipzig, Germany.
  • 8 Interdisciplinary Centre for Bioinformatics, University of Leipzig, 04107 Leipzig, Germany.
  • 9 Translational Centre for Regenerative Medicine Leipzig, University of Leipzig, 04103 Leipzig, Germany Institute of Biology, Division of Cell and Developmental Biology, University of Leipzig, 04103 Leipzig, Germany thomas.magin@uni-leipzig.de.
PMID: 26644517 DOI: 10.1083/jcb.201404147
Abstract

Keratin intermediate filaments (KIFs) protect the epidermis against mechanical force, support strong adhesion, help barrier formation, and regulate growth. The mechanisms by which type I and II keratins contribute to these functions remain incompletely understood. Here, we report that mice lacking all type I or type II keratins display severe barrier defects and fragile skin, leading to perinatal mortality with full penetrance. Comparative proteomics of cornified envelopes (CEs) from prenatal KtyI(-/-) and KtyII(-/-)(K8) mice demonstrates that absence of KIF causes dysregulation of many CE constituents, including downregulation of desmoglein 1. Despite persistence of loricrin expression and upregulation of many Nrf2 targets, including CE components Sprr2d and Sprr2h, extensive barrier defects persist, identifying keratins as essential CE scaffolds. Furthermore, we show that KIFs control mitochondrial lipid composition and activity in a cell-intrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation.

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