FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism

Research output: Contribution to journalJournal articleResearchpeer-review

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, C Ronald Kahn

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.

Original languageEnglish
JournalNature Communications
Volume10
Issue number1
Pages (from-to)1582
ISSN2041-1723
DOIs
Publication statusPublished - 5 Apr 2019

ID: 216343824