Keratins regulate β-cell mitochondrial morphology, motility, and homeostasis

FASEB J. 2017 Oct;31(10):4578-4587. doi: 10.1096/fj.201700095R. Epub 2017 Jun 30.


Loss of the epithelial intermediate filament protein keratin 8 (K8) in murine β cells leads to irregular insulin vesicles and decreased insulin levels. Because mitochondria are central in glucose-stimulated insulin secretion, the relationship between keratins and β-cell mitochondrial function and morphology was investigated. β cells in murine K8-knockout (K8-/-) islets of Langerhans have increased numbers of mitochondria, which are rounder and have diffuse cristae, as seen by electron microscopy. The mitochondrial network in primary cultured K8-/- β cells is more fragmented compared with K8+/+ mitochondria, correlating with decreased levels of mitofusin 2 and the mitofusin 2- and keratin-binding protein trichoplein. K8-/- β-cell mitochondria have decreased levels of total and mitochondrial cytochrome c, which correlates with a reduction in electron transport complexes I and IV. This provokes loss of mitochondrial membrane potential and reduction of ATP and insulin amount, as seen in K8-/- β cells. Mitochondria in K8 wild-type β cells and MIN6 insulinoma cells overexpressing K8 and 18 are more stationary compared with mitochondria in keratin-deficient cells. In conclusion, keratins, likely through trichoplein-mitofusin interactions, regulate both structural and dynamic functions of β-cell mitochondria, which could have implications for downstream insulin secretion.-Silvander, J. S. G., Kvarnström, S. M., Kumari-Ilieva, A., Shrestha, A., Alam, C. M., Toivola, D. M. Keratins regulate β-cell mitochondrial morphology, motility, and homeostasis.

Keywords: K8-null mice; TEM; fusion; insulin secretion; islets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / physiology*
  • Cell Shape
  • Cells, Cultured
  • Cytochromes c / metabolism
  • Hepatocytes / metabolism
  • Homeostasis / physiology*
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism*
  • Intermediate Filament Proteins / metabolism
  • Intermediate Filaments / metabolism
  • Keratin-8 / deficiency
  • Keratin-8 / metabolism*
  • Mice, Knockout
  • Mitochondria / genetics
  • Mitochondria / metabolism*


  • Intermediate Filament Proteins
  • Keratin-8
  • Cytochromes c