TY - JOUR
T1 - Peroxides and peroxidases in the endoplasmic reticulum
T2 - Integrating redox homeostasis and oxidative folding
AU - Kakihana, Taichi
AU - Nagata, Kazuhiro
AU - Sitia, Roberto
PY - 2012/4/15
Y1 - 2012/4/15
N2 - Significance: The endoplasmic reticulum (ER), the port of entry into the secretory pathway, is a complex organelle that performs many fundamental functions, including protein synthesis and quality control, Ca
2+ storage and signaling. Redox homeostasis is of paramount importance for allowing the efficient folding of secretory proteins, most of which contain essential disulfide bonds. Recent Advances: revealed that an intricate protein network sustains the processes of disulfide bond formation and reshuffling in the ER. Remarkably, H
2O
2, which is a known by-product of Ero1 flavoproteins in cells, is utilized by peroxiredoxin-4 and glutathione peroxidases-7 and -8, which reside in the mammalian secretory compartment and further fuel oxidative protein folding while limiting oxidative damage. Critical Issues: that remain to be addressed are the sources, diffusibility and signaling role(s) of H
2O
2 in and between organelles and cells, how the emerging redundancy in the systems is coupled to precise regulation, and how the distinct pathways operating in the early secretory compartment are integrated with one another. Future Directions: A further dissection of the pathways that integrate folding, redox homeostasis, and signaling in the early secretory pathway may allow to manipulate protein homeostasis and survival-death decisions in degenerative diseases or cancer. Antioxid. Redox Signal. 16, 763-771.
AB - Significance: The endoplasmic reticulum (ER), the port of entry into the secretory pathway, is a complex organelle that performs many fundamental functions, including protein synthesis and quality control, Ca
2+ storage and signaling. Redox homeostasis is of paramount importance for allowing the efficient folding of secretory proteins, most of which contain essential disulfide bonds. Recent Advances: revealed that an intricate protein network sustains the processes of disulfide bond formation and reshuffling in the ER. Remarkably, H
2O
2, which is a known by-product of Ero1 flavoproteins in cells, is utilized by peroxiredoxin-4 and glutathione peroxidases-7 and -8, which reside in the mammalian secretory compartment and further fuel oxidative protein folding while limiting oxidative damage. Critical Issues: that remain to be addressed are the sources, diffusibility and signaling role(s) of H
2O
2 in and between organelles and cells, how the emerging redundancy in the systems is coupled to precise regulation, and how the distinct pathways operating in the early secretory compartment are integrated with one another. Future Directions: A further dissection of the pathways that integrate folding, redox homeostasis, and signaling in the early secretory pathway may allow to manipulate protein homeostasis and survival-death decisions in degenerative diseases or cancer. Antioxid. Redox Signal. 16, 763-771.
UR - http://www.scopus.com/inward/record.url?scp=84857602613&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857602613&partnerID=8YFLogxK
U2 - 10.1089/ars.2011.4238
DO - 10.1089/ars.2011.4238
M3 - Article
C2 - 22146055
AN - SCOPUS:84857602613
VL - 16
SP - 763
EP - 771
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 8
ER -