Akt regulation of glycolysis mediates bioenergetic stability in epithelial cells

作者：Hung Yin P.; Teragawa Carolyn; Kosaisawe Nont; Gillies Taryn E.; Pargett Michael; Minguet Marta; Distor Kevin; Rocha-Gregg Briana L.; Coloff Jonathan L.; Keibler Mark A.; Stephanopoulos Gregory; Yellen Gary; Brugge Joan S.; Albeck John G.^*

来源：eLife, 2017, 6: e27293.

DOI：10.7554/eLife.27293

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.

• 出版日期2017-12-14