Fig. 4
From: Research progress on multiple cell death pathways of podocytes in diabetic kidney disease
ER Stress-related pathway. ER stress mainly consists of three signaling pathways activated by three protein sensors, including activating transcription factor 6 (ATF6), inositol requirement enzyme 1α (IRE1α), and PRKR-like ER kinase (PERK). First, ATF6 moves to the Golgi apparatus, where it is sequentially cut by S1P and S2P. Subsequently activated ATF6 fragments mediate the expression of CHOP and several components of ER-associated degradation (ERAD). Second, IRE1α activation mediates the unconventional splicing of XBP1 mRNA. Spliced XBP1 (XBP1s) is involved in glucose metabolism, lipid biosynthesis, and DNA damage. Finally, activated PERK phosphorylates eIF2α, which is involved in ATP depletion, oxidative stress, and apoptosis