Figure 2. Graphical abstract summarizing how AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin. Schematic showing the pertinent findings reported in by Aznar et al. . Top (from left to right): In normal physiologic states, sheets of polarized epithelial cells maintain barrier integrity by assembling tight junctions [TJs; stained here with the TJ-marker and integral membrane protein, Occludin in green]. Exposure to energetic stress triggers the activation of AMPK, a sensor of cellular energy stores, which in turn phosphorylates GIV at Ser245. Phospho-GIV [stained red] localizes to the TJs [marked with occluding] and serves to stabilize TJs and resist stress-induced collapse. Bottom: Schematic summarizing how the AMPK-GIV signaling axis preserves TJ integrity via multiple interacting partners of the polarity scaffold, GIV, and how this stress-polarity pathway enhances barrier functions and inhibits neoplastic transformation.