Stress on redox

Abstract 

Redox imbalance in the endoplasmic reticulum lumen is the most frequent cause of endoplasmic reticulum stress and consequent apoptosis. The mechanism involves the impairment of oxidative protein folding, the accumulation of unfolded/misfolded proteins in the lumen and the initiation of the unfolded protein response. The participation of several redox systems (glutathione, ascorbate, FAD, tocopherol, vitamin K) has been demonstrated in the process. Recent findings have attracted attention to the possible mechanistic role of luminal pyridine nucleotides in the endoplasmic reticulum stress. The aim of this minireview is to summarize the luminal redox systems and the redox sensing mechanisms of the endoplasmic reticulum.

Abbreviations: ATF6, activating transcription factor 6, BiP, immunoglobulin heavy chain-binding protein, DHAR, dehydroascorbate reductase, ER, endoplasmic reticulum, Ero1, endoplasmic reticulum oxidoreductin 1, ERp44 and 57, endoplasmic reticulum protein of molecular weight 44 or 57kDa, GRP78, glucose-regulated protein of molecular weight 78kDa, G6PT, glucose-6-phosphate transporter, H6PDH, hexose-6-phosphate dehydrogenase, 11βHSD1, 11β-hydroxysteroid dehydrogenase type 1, InsP3R, inositol 1,4,5-trisphosphate receptor, IRE1, inositol-requiring enzyme 1, PDI, protein disulfide isomerase, PERK/PEK, PKR-like ER protein kinase/pancreatic eIF2α (eukaryotic translation initiation factor 2, α subunit) kinase, SERCA, sarco/endoplasmic reticulum Ca²⁺-ATPase, UPR, unfolded protein response

Keywords: Endoplasmic reticulum, Oxidative protein folding, Unfolded protein response, Glutathione, NADPH, Ascorbate