English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism

MPS-Authors
/persons/resource/persons195396

Steger,  Martin
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons192037

Albrechtsen,  Nicolai J. Wewer
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78356

Mann,  Matthias
Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)

s41467-019-09418-0.pdf
(Publisher version), 5MB

Supplementary Material (public)

41467_2019_9418_MOESM1_ESM.pdf
(Supplementary material), 5MB

Citation

Sakaguchi, M., Cai, W., Wang, C.-H., Cederquist, C. T., Damasio, M., Homan, E. P., et al. (2019). FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. Nature Communications, 10: 1582. doi:10.1038/s41467-019-09418-0.


Cite as: https://hdl.handle.net/21.11116/0000-0003-E692-4
Abstract
A major target of insulin signaling is the FoxO family of Forkhead transcription factors, which translocate from the nucleus to the cytoplasm following insulin-stimulated phosphorylation. Here we show that the Forkhead transcription factors FoxK1 and FoxK2 are also downstream targets of insulin action, but that following insulin stimulation, they translocate from the cytoplasm to nucleus, reciprocal to the translocation of FoxO1. FoxK1/FoxK2 translocation to the nucleus is dependent on the Akt-mTOR pathway, while its localization to the cytoplasm in the basal state is dependent on GSK3. Knockdown of FoxK1 and FoxK2 in liver cells results in upregulation of genes related to apoptosis and down-regulation of genes involved in cell cycle and lipid metabolism. This is associated with decreased cell proliferation and altered mitochondrial fatty acid metabolism. Thus, FoxK1/K2 are reciprocally regulated to FoxO1 following insulin stimulation and play a critical role in the control of apoptosis, metabolism and mitochondrial function.