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

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, Christina B. Brazel, Sandra Heller, Hans Binder, Henry Löffler-Wirth, Peter Seibel, Thomas M. Magin

Research output: Contribution to journalArticle

39 Scopus citations

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 cellintrinsic manner. Therefore, our study explains the complexity of keratinopathies accompanied by barrier disorders by linking keratin scaffolds to mitochondria, adhesion, and CE formation.

Original languageEnglish (US)
Pages (from-to)1057-1075
Number of pages19
JournalJournal of Cell Biology
Volume211
Issue number5
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Cell Biology

Fingerprint Dive into the research topics of 'A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity'. Together they form a unique fingerprint.

Cite this