FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism

Masaji Sakaguchi, Weikang Cai, Chih-Hao Wang, Carly T. Cederquist, Marcos Damasio, Erica P. Homan, Thiago Batista, Alfred K. Ramirez, Manoj K. Gupta, Martin Steger, Nicolai J. Wewer Albrechtsen, Shailendra Kumar Singh, Eiichi Araki, Matthias Mann, Sven Enerbäck and C. Ronald Kahn ()
Additional contact information
Masaji Sakaguchi: Joslin Diabetes Center
Weikang Cai: Joslin Diabetes Center
Chih-Hao Wang: Joslin Diabetes Center
Carly T. Cederquist: Joslin Diabetes Center
Marcos Damasio: Joslin Diabetes Center
Erica P. Homan: Joslin Diabetes Center
Thiago Batista: Joslin Diabetes Center
Alfred K. Ramirez: Joslin Diabetes Center
Manoj K. Gupta: Joslin Diabetes Center
Martin Steger: Max Planck Institute of Biochemistry
Nicolai J. Wewer Albrechtsen: Max Planck Institute of Biochemistry
Shailendra Kumar Singh: The World Premier International Research Center Initiative Immunology Frontier Research Center
Eiichi Araki: Kumamoto University
Matthias Mann: Max Planck Institute of Biochemistry
Sven Enerbäck: University of Gothenburg
C. Ronald Kahn: Joslin Diabetes Center

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-019-09418-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09418-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-09418-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().