Figure 14.
Cytoprotective effects of H2S during ER stress in hepatocytes. Persistent SERCA channel inhibition by thapsigargin provokes aberrant activation of the UPR effectors–PERK, ATF6, and IRE1α–that results in the ectopic expression of the pro-apoptotic Chop, autophagic arrest, bioenergetic crisis, and ultimately, cell death. Restoration of H2S levels resolves the “terminal UPR” and preserves mitochondrial function and autophagosome formation to swift hepatic cell fate towards survival. For further mechanistic details, please see the main text.