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Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation
Journal article   Open access   Peer reviewed

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

Anthony J Covarrubias, Halil Ibrahim Aksoylar, Jiujiu Yu, Nathaniel W Snyder, Andrew J Worth, Shankar S Iyer, Jiawei Wang, Issam Ben-Sahra, Vanessa Byles, Tiffany Polynne-Stapornkul, …
eLife, v 5(2016)
19 Feb 2016
PMID: 26894960
url
https://doi.org/10.7554/elife.11612View
Published, Version of Record (VoR)CC BY V4.0 Open
url
https://doi.org/10.7554/eLife.11612View
Published, Version of Record (VoR) Open

Abstract

Acetylation Animals ATP Citrate (pro-S)-Lyase - metabolism Cell Proliferation Chemokines - metabolism Gene Expression Regulation Histones - metabolism Interleukin-4 - metabolism Macrophage Activation Macrophages - metabolism Macrophages - physiology Mechanistic Target of Rapamycin Complex 1 Mice, Inbred C57BL Multiprotein Complexes - metabolism Protein Processing, Post-Translational Proto-Oncogene Proteins c-akt - metabolism Signal Transduction TOR Serine-Threonine Kinases - metabolism ESI Highly Cited Paper (Incites)
Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biology
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