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; Erika C Espinosa; Dudley Lamming; Brendan D Manning; Yijing Zhang; Ian A Blair; Tiffany Horng

doi:10.7554/eLife.11612

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

Journal article

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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

DOI: https://doi.org/10.7554/eLife.11612

PMID: 26894960

Featured in Collection : UN Sustainable Development Goals @ Drexel

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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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383 citations in Scopus

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Title: Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation
Creators: Anthony J Covarrubias - Harvard University
Halil Ibrahim Aksoylar - Harvard University
Jiujiu Yu - Harvard University
Nathaniel W Snyder - Drexel University
Andrew J Worth - University of Pennsylvania
Shankar S Iyer - Brigham and Women's Hospital
Jiawei Wang - Shanghai Institutes for Biological Sciences
Issam Ben-Sahra - Harvard University
Vanessa Byles - Harvard University
Tiffany Polynne-Stapornkul - Harvard University
Erika C Espinosa - Harvard University
Dudley Lamming - University of Wisconsin–Madison
Brendan D Manning - Harvard University
Yijing Zhang - Shanghai Institutes for Biological Sciences
Ian A Blair - University of Pennsylvania
Tiffany Horng - Harvard University
Publication Details: eLife, v 5(2016)
Publisher: eLife
Grant note: K99 AG041765 / NIA NIH HHS R35CA197459 / NCI NIH HHS R01 AI102964 / NIAID NIH HHS T32 DK007260 / NIDDK NIH HHS P30 ES013508 / NIEHS NIH HHS R35 CA197459 / NCI NIH HHS T32 ES019851 / NIEHS NIH HHS R21 AI119763 / NIAID NIH HHS R01AI102964 / NIAID NIH HHS R00 AG041765 / NIA NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: A.J. Drexel Autism Institute
Web of Science ID: WOS:000371881300001
Scopus ID: 2-s2.0-84961281785
Other Identifier: 991019167905704721

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Highly Cited Paper

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

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

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UN Sustainable Development Goals (SDGs)

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