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.
journal_name
Elifejournal_title
eLifeauthors
Hung YP,Teragawa C,Kosaisawe N,Gillies TE,Pargett M,Minguet M,Distor K,Rocha-Gregg BL,Coloff JL,Keibler MA,Stephanopoulos G,Yellen G,Brugge JS,Albeck JGdoi
10.7554/eLife.27293subject
Has Abstractpub_date
2017-12-14 00:00:00issn
2050-084Xpii
27293journal_volume
6pub_type
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