Figure 2.

The PCr/Cr shuttle promotes mucosal barrier and wound healing by improving cellular energetics and by stabilization of the adherence junctions. During active inflammation, such as that seen in IBD, low O₂ levels result in the stabilization of HIF and resultant induction of creatine kinase (CK) isoenzymes and the Cr transporter (CrT1) within intestinal epithelial cells (see [16,62,63] for further details). CK localizes to epithelial junctions that are stabilized by interactions with the actin cytoskeleton. In response to epithelial disruption during inflammation, large amounts of ATP are necessary to accommodate the demand for cytoskeletal reorganization, including the acto-myosin ATPase at epithelial cellular junctions. Under such conditions, CK and CrT1 coordinately promote wound healing and barrier function by generating ATP from PCr to efficiently promote homeostasis.