Adams, WC, Chen, Y-H, Kratchmarov, R et al. (10 more authors) (2016) Anabolism-Associated Mitochondrial Stasis Driving Lymphocyte Differentiation over Self-Renewal. Cell Reports, 17 (12). pp. 3142-3152. ISSN 2211-1247
Abstract
Regeneration requires related cells to diverge in fate. We show that activated lymphocytes yield sibling cells with unequal elimination of aged mitochondria. Disparate mitochondrial clearance impacts cell fate and reflects larger constellations of opposing metabolic states. Differentiation driven by an anabolic constellation of PI3K/mTOR activation, aerobic glycolysis, inhibited autophagy, mitochondrial stasis, and ROS production is balanced with self-renewal maintained by a catabolic constellation of AMPK activation, mitochondrial elimination, oxidative metabolism, and maintenance of FoxO1 activity. Perturbations up and down the metabolic pathways shift the balance of nutritive constellations and cell fate owing to self-reinforcement and reciprocal inhibition between anabolism and catabolism. Cell fate and metabolic state are linked by transcriptional regulators, such as IRF4 and FoxO1, with dual roles in lineage and metabolic choice. Instructing some cells to utilize nutrients for anabolism and differentiation while other cells catabolically self-digest and self-renew may enable growth and repair in metazoa.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 The Author(s). Published by Elsevier. The article was published under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International. |
Keywords: | Asymmetric cell division; TCF1; Pax5; Warburg effect; stem cell; self-renewal |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Experimental Haematology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Jan 2017 14:44 |
Last Modified: | 05 Oct 2017 16:21 |
Published Version: | http://dx.doi.org/10.1016/j.celrep.2016.11.065 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.celrep.2016.11.065 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:111316 |