Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells
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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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eLife Sciences Publications, Ltd
2018
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| Online Access: | http://hdl.handle.net/1721.1/113029 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0001-6909-4568 |
| _version_ | 1826197428009697280 |
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| author | 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 Brugge, Joan S Albeck, John G Keibler, Mark Andrew Stephanopoulos, Gregory |
| author2 | Keibler, Mark Andrew |
| author_facet | Keibler, Mark Andrew 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 Brugge, Joan S Albeck, John G Keibler, Mark Andrew Stephanopoulos, Gregory |
| author_sort | Hung, Yin P |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:47:31Z |
| format | Article |
| id | mit-1721.1/113029 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T10:47:31Z |
| publishDate | 2018 |
| publisher | eLife Sciences Publications, Ltd |
| record_format | dspace |
| spelling | mit-1721.1/1130292019-05-17T09:22:51Z Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells 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 Brugge, Joan S Albeck, John G Keibler, Mark Andrew Stephanopoulos, Gregory Keibler, Mark Andrew Stephanopoulos, Gregory 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. 2018-01-08T20:47:46Z 2018-01-08T20:47:46Z 2017-12 2017-03 2018-01-08T19:37:47Z Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/113029 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 PUBLISHER_CC https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0001-6909-4568 http://dx.doi.org/10.7554/eLife.27293 eLife Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ application/octet-stream eLife Sciences Publications, Ltd eLife |
| spellingShingle | 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 Brugge, Joan S Albeck, John G Keibler, Mark Andrew Stephanopoulos, Gregory Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title | Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title_full | Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title_fullStr | Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title_full_unstemmed | Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title_short | Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| title_sort | akt regulation of glycolysis mediates bioenergetic stability in epithelial cells |
| url | http://hdl.handle.net/1721.1/113029 https://orcid.org/0000-0002-5410-6543 https://orcid.org/0000-0001-6909-4568 |
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