AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR. / Collodet, Caterina; Foretz, Marc; Deak, Maria; Bultot, Laurent; Metairon, Sylviane; Viollet, Benoit; Lefebvre, Gregory; Raymond, Frederic; Parisi, Alice; Civiletto, Gabriele; Gut, Philipp; Descombes, Patrick; Sakamoto, Kei.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 11, 11.2019, p. 12374-12391.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Collodet, C, Foretz, M, Deak, M, Bultot, L, Metairon, S, Viollet, B, Lefebvre, G, Raymond, F, Parisi, A, Civiletto, G, Gut, P, Descombes, P & Sakamoto, K 2019, 'AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol. 33, no. 11, pp. 12374-12391. https://doi.org/10.1096/fj.201900841R

APA

Collodet, C., Foretz, M., Deak, M., Bultot, L., Metairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., Gut, P., Descombes, P., & Sakamoto, K. (2019). AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 33(11), 12374-12391. https://doi.org/10.1096/fj.201900841R

Vancouver

Collodet C, Foretz M, Deak M, Bultot L, Metairon S, Viollet B et al. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 Nov;33(11):12374-12391. https://doi.org/10.1096/fj.201900841R

Author

Collodet, Caterina ; Foretz, Marc ; Deak, Maria ; Bultot, Laurent ; Metairon, Sylviane ; Viollet, Benoit ; Lefebvre, Gregory ; Raymond, Frederic ; Parisi, Alice ; Civiletto, Gabriele ; Gut, Philipp ; Descombes, Patrick ; Sakamoto, Kei. / AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 11. pp. 12374-12391.

Bibtex

@article{de19c72a88cd41e49a4189a00eb59f4a,
title = "AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR",
abstract = "AMPK is a central regulator of energy homeostasis. AMPK not only elicits acute metabolic responses but also promotes metabolic reprogramming and adaptations in the long-term through regulation of specific transcription factors and coactivators. We performed a whole-genome transcriptome profiling in wild-type (WT) and AMPK-deficient mouse embryonic fibroblasts (MEFs) and primary hepatocytes that had been treated with 2 distinct classes of small-molecule AMPK activators. We identified unique compound-dependent gene expression signatures and several AMPK-regulated genes, including folliculin (Flcn), which encodes the tumor suppressor FLCN. Bioinformatics analysis highlighted the lysosomal pathway and the associated transcription factor EB (TFEB) as a key transcriptional mediator responsible for AMPK responses. AMPK-induced Flcn expression was abolished in MEFs lacking TFEB and transcription factor E3, 2 transcription factors with partially redundant function; additionally, the promoter activity of Flcn was profoundly reduced when its putative TFEB-binding site was mutated. The AMPK-TFEB-FLCN axis is conserved across species; swimming exercise in WT zebrafish induced Flcn expression in muscle, which was significantly reduced in AMPK-deficient zebrafish. Mechanistically, we have found that AMPK promotes dephosphorylation and nuclear localization of TFEB independently of mammalian target of rapamycin activity. Collectively, we identified the novel AMPK-TFEB-FLCN axis, which may function as a key cascade for cellular and metabolic adaptations.-Collodet, C., Foretz, M., Deak, M., Bultot, L., Metairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., Gut, P., Descombes, P., Sakamoto, K. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR.",
author = "Caterina Collodet and Marc Foretz and Maria Deak and Laurent Bultot and Sylviane Metairon and Benoit Viollet and Gregory Lefebvre and Frederic Raymond and Alice Parisi and Gabriele Civiletto and Philipp Gut and Patrick Descombes and Kei Sakamoto",
year = "2019",
month = nov,
doi = "10.1096/fj.201900841R",
language = "English",
volume = "33",
pages = "12374--12391",
journal = "F A S E B Journal",
issn = "0892-6638",
publisher = "Federation of American Societies for Experimental Biology",
number = "11",

}

RIS

TY - JOUR

T1 - AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR

AU - Collodet, Caterina

AU - Foretz, Marc

AU - Deak, Maria

AU - Bultot, Laurent

AU - Metairon, Sylviane

AU - Viollet, Benoit

AU - Lefebvre, Gregory

AU - Raymond, Frederic

AU - Parisi, Alice

AU - Civiletto, Gabriele

AU - Gut, Philipp

AU - Descombes, Patrick

AU - Sakamoto, Kei

PY - 2019/11

Y1 - 2019/11

N2 - AMPK is a central regulator of energy homeostasis. AMPK not only elicits acute metabolic responses but also promotes metabolic reprogramming and adaptations in the long-term through regulation of specific transcription factors and coactivators. We performed a whole-genome transcriptome profiling in wild-type (WT) and AMPK-deficient mouse embryonic fibroblasts (MEFs) and primary hepatocytes that had been treated with 2 distinct classes of small-molecule AMPK activators. We identified unique compound-dependent gene expression signatures and several AMPK-regulated genes, including folliculin (Flcn), which encodes the tumor suppressor FLCN. Bioinformatics analysis highlighted the lysosomal pathway and the associated transcription factor EB (TFEB) as a key transcriptional mediator responsible for AMPK responses. AMPK-induced Flcn expression was abolished in MEFs lacking TFEB and transcription factor E3, 2 transcription factors with partially redundant function; additionally, the promoter activity of Flcn was profoundly reduced when its putative TFEB-binding site was mutated. The AMPK-TFEB-FLCN axis is conserved across species; swimming exercise in WT zebrafish induced Flcn expression in muscle, which was significantly reduced in AMPK-deficient zebrafish. Mechanistically, we have found that AMPK promotes dephosphorylation and nuclear localization of TFEB independently of mammalian target of rapamycin activity. Collectively, we identified the novel AMPK-TFEB-FLCN axis, which may function as a key cascade for cellular and metabolic adaptations.-Collodet, C., Foretz, M., Deak, M., Bultot, L., Metairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., Gut, P., Descombes, P., Sakamoto, K. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR.

AB - AMPK is a central regulator of energy homeostasis. AMPK not only elicits acute metabolic responses but also promotes metabolic reprogramming and adaptations in the long-term through regulation of specific transcription factors and coactivators. We performed a whole-genome transcriptome profiling in wild-type (WT) and AMPK-deficient mouse embryonic fibroblasts (MEFs) and primary hepatocytes that had been treated with 2 distinct classes of small-molecule AMPK activators. We identified unique compound-dependent gene expression signatures and several AMPK-regulated genes, including folliculin (Flcn), which encodes the tumor suppressor FLCN. Bioinformatics analysis highlighted the lysosomal pathway and the associated transcription factor EB (TFEB) as a key transcriptional mediator responsible for AMPK responses. AMPK-induced Flcn expression was abolished in MEFs lacking TFEB and transcription factor E3, 2 transcription factors with partially redundant function; additionally, the promoter activity of Flcn was profoundly reduced when its putative TFEB-binding site was mutated. The AMPK-TFEB-FLCN axis is conserved across species; swimming exercise in WT zebrafish induced Flcn expression in muscle, which was significantly reduced in AMPK-deficient zebrafish. Mechanistically, we have found that AMPK promotes dephosphorylation and nuclear localization of TFEB independently of mammalian target of rapamycin activity. Collectively, we identified the novel AMPK-TFEB-FLCN axis, which may function as a key cascade for cellular and metabolic adaptations.-Collodet, C., Foretz, M., Deak, M., Bultot, L., Metairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., Gut, P., Descombes, P., Sakamoto, K. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR.

U2 - 10.1096/fj.201900841R

DO - 10.1096/fj.201900841R

M3 - Journal article

C2 - 31404503

VL - 33

SP - 12374

EP - 12391

JO - F A S E B Journal

JF - F A S E B Journal

SN - 0892-6638

IS - 11

ER -

ID: 239474913