Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells
Name
Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells
Size
5.95 MB
Format
Unknown
Checksum (MD5)
52b0e27d6093f0c6d50d78a75afad5f5
Author(s)
Hung, Yin P
Teragawa, Carolyn
Kosaisawe, Nont
Gillies, Taryn E
Pargett, Michael
Minguet, Marta
Distor, Kevin
Rocha-Gregg, Briana L
Coloff, Jonathan L
Yellen, Gary
Date Issued
December 2017
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
Hung, Yin P et al. “Akt Regulation of Glycolysis Mediates Bioenergetic Stability in Epithelial Cells.” eLife 2017, 6 (December 2017): e27293 © 2017 Hung et al
Version
Final published version
Abstract
Cells use multiple feedback controls to regulate metabolism in response to nutrient and signaling inputs. However, feedback creates the potential for unstable network responses. We examined how concentrations of key metabolites and signaling pathways interact to maintain homeostasis in proliferating human cells, using fluorescent reporters for AMPK activity, Akt activity, and cytosolic NADH/NAD⁺ redox. Across various conditions, including glycolytic or mitochondrial inhibition or cell proliferation, we observed distinct patterns of AMPK activity, including both stable adaptation and highly dynamic behaviors such as periodic oscillations and irregular fluctuations that indicate a failure to reach a steady state. Fluctuations in AMPK activity, Akt activity, and cytosolic NADH/NAD⁺ redox state were temporally linked in individual cells adapting to metabolic perturbations. By monitoring single-cell dynamics in each of these contexts, we identified PI3K/Akt regulation of glycolysis as a multifaceted modulator of single-cell metabolic dynamics that is required to maintain metabolic stability in proliferating cells.
Terms of Use
Creative Commons Attribution 4.0 International
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.7554/eLife.27293
