Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Dec 14, 2017
- Source ID
- 10.7554/elife.27293
Entities
People
- Briana L Rocha-gregg
- Carolyn Teragawa
- Gary Yellen
- Gregory Stephanopoulos
- Joan Brugge
- John G Albeck
- Jonathan L Coloff
- Kevin Distor
- Mark A Keibler
- Marta Minguet
- Michael Pargett
- Nont Kosaisawe
- Taryn E. Gillies
- Yin Pun Hung
Organizations
- Brigham and Women's Hospital
- Congressionally Directed Medical Research Programs
- Harvard Medical School
- Massachusetts Institute of Technology
- National Cancer Institute
- National Institute of Neurological Disorders and Stroke
- University of California