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

keratin intermediate filaments epidermal barrier mitochondrial lipid composition type I keratins type II keratins cornified envelope desmoglein 1 loricrin Nrf2 keratinopathies

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 and mitochondrial function using keratin-deficient mouse models. Mice lacking specific keratins exhibited severe barrier defects, fragile skin, and perinatal mortality, underscoring the essential role of KIFs in maintaining epidermal integrity. Despite upregulation of Nrf2 target genes, compensatory mechanisms failed to restore barrier function, highlighting the importance of keratins in coordinating cornified envelope (CE) protein assembly. Additionally, keratin deficiency led to altered mitochondrial lipid composition and increased mitochondrial activity, linking keratins to energy metabolism. The findings provided insights into the molecular mechanisms of keratinopathies and barrier disorders, suggesting that keratin mutations could predispose individuals to inflammatory skin conditions.

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