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

28 Citations (Scopus)

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

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Keratins
Intermediate Filaments
Lipids
Type II Keratin
Type I Keratin
Desmoglein 1
Penetrance
Perinatal Mortality
Epidermis
Proteomics
Mitochondria
Up-Regulation
Down-Regulation
Skin
Growth

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kumar, V., Bouameur, J. E., Bär, J., Rice, R. H., Hornig-Do, H. T., Roop, D. R., ... Magin, T. M. (2015). A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. Journal of Cell Biology, 211(5), 1057-1075. https://doi.org/10.1083/jcb.201404147

A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. / Kumar, Vinod; Bouameur, Jamal Eddine; Bär, Janina; Rice, Robert H.; Hornig-Do, Hue Tran; Roop, Dennis R.; Schwarz, Nicole; Brodesser, Susanne; Thiering, Sören; Leube, Rudolf E.; Wiesner, Rudolf J.; Brazel, Christina B.; Heller, Sandra; Binder, Hans; Löffler-Wirth, Henry; Seibel, Peter; Magin, Thomas M.

In: Journal of Cell Biology, Vol. 211, No. 5, 2015, p. 1057-1075.

Research output: Contribution to journalArticle

Kumar, V, Bouameur, JE, Bär, J, Rice, RH, Hornig-Do, HT, Roop, DR, Schwarz, N, Brodesser, S, Thiering, S, Leube, RE, Wiesner, RJ, Brazel, CB, Heller, S, Binder, H, Löffler-Wirth, H, Seibel, P & Magin, TM 2015, 'A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity', Journal of Cell Biology, vol. 211, no. 5, pp. 1057-1075. https://doi.org/10.1083/jcb.201404147
Kumar, Vinod ; Bouameur, Jamal Eddine ; Bär, Janina ; Rice, Robert H. ; Hornig-Do, Hue Tran ; Roop, Dennis R. ; Schwarz, Nicole ; Brodesser, Susanne ; Thiering, Sören ; Leube, Rudolf E. ; Wiesner, Rudolf J. ; Brazel, Christina B. ; Heller, Sandra ; Binder, Hans ; Löffler-Wirth, Henry ; Seibel, Peter ; Magin, Thomas M. / A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. In: Journal of Cell Biology. 2015 ; Vol. 211, No. 5. pp. 1057-1075.
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