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

Silvander, Jonas S. G.; Kvarnström, Sofie M.; Kumari‐Ilieva, Angeli; Shrestha, Anup; Alam, Catharina M.; Toivola, Diana M.


Jonas S. G. Silvander

Sofie M. Kvarnström

Angeli Kumari‐Ilieva

Anup Shrestha

Diana M. Toivola


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. (2017). Keratins regulate β‐cell mitochondrial morphology, motility, and homeostasis. FASEB Journal, 31(10), 4578-4587.

Journal Article Type Article
Acceptance Date Jun 19, 2017
Online Publication Date Sep 19, 2017
Publication Date 2017-10
Deposit Date Nov 14, 2022
Journal The FASEB Journal
Print ISSN 0892-6638
Electronic ISSN 1530-6860
Publisher Federation of American Society of Experimental Biology
Peer Reviewed Peer Reviewed
Volume 31
Issue 10
Pages 4578-4587
Keywords TEM, insulin secretion, islets, K8-null mice, fusion
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