FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism. / Sakaguchi, Masaji; Cai, Weikang; Wang, Chih-Hao; Cederquist, Carly T; Damasio, Marcos; Homan, Erica P; Batista, Thiago; Ramirez, Alfred K; Gupta, Manoj K; Steger, Martin; Wewer Albrechtsen, Nicolai J; Singh, Shailendra Kumar; Araki, Eiichi; Mann, Matthias; Enerbäck, Sven; Kahn, C Ronald.
In: Nature Communications, Vol. 10, No. 1, 1582, 05.04.2019.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - FoxK1 and FoxK2 in insulin regulation of cellular and mitochondrial metabolism
AU - Sakaguchi, Masaji
AU - Cai, Weikang
AU - Wang, Chih-Hao
AU - Cederquist, Carly T
AU - Damasio, Marcos
AU - Homan, Erica P
AU - Batista, Thiago
AU - Ramirez, Alfred K
AU - Gupta, Manoj K
AU - Steger, Martin
AU - Wewer Albrechtsen, Nicolai J
AU - Singh, Shailendra Kumar
AU - Araki, Eiichi
AU - Mann, Matthias
AU - Enerbäck, Sven
AU - Kahn, C Ronald
PY - 2019/4/5
Y1 - 2019/4/5
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-019-09418-0
DO - 10.1038/s41467-019-09418-0
M3 - Journal article
C2 - 30952843
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 1582
ER -
ID: 216343824