Endoplasmic Reticulum Stress
The endoplasmic reticulum serves many general functions, including the folding of protein molecules in sacs called cisternae and the transport of synthesized proteins in vesicles to the Golgi apparatus. The function of the rough ER is to provide a place so ribosomes can produce proteins, and proteins are one of the most important things in a cell. Rough ER is the organelle that reads the DNA instructions to make the proteins. Additionally, the rough ER makes certain enzymes that are vital to the cells. Disturbance in any of these functions, which results in the disruption of the proper folding and secretory capacity of the ER and increased load of unfolded proteins in its lumen, defines a condition known as “ER stress”.
The Endoplasmic Reticulum stress occurs when the capacity of the ER to fold proteins becomes saturated. ER stress may be caused by factors that impair protein glycosylation or disulfide bond formation, or by overexpression of or mutations in proteins entering the secretory pathway. ER stress can also be induced by hypoxia.
Inability to restore ER functions induces cell death, which is usually in the form of apoptosis. The ER stress response is initiated when the capacity of ER-resident chaperone proteins is exceeded by the load of misfolded proteins. Protein chaperones like BiP/GRP78, Grp 94, and calreticulin assist in proper protein folding. BiP/GRP78, a transmembrane protein that spans the ER lumen, associates with the UPR sensors ATF6, IRE1, and PERK and represses their activity. The accumulation of misfolded proteins results in the saturation of ER chaperones, including BiP/GRP78. The sequestering of BiP by misfolded proteins results in the loss of BiP-mediated repression of the UPR sensors resulting in their activation. Prolonged ER stress typically results in cell death by apoptosis.
Endoplasmic reticulum stress and other biomedical related manuscripts are accepted to publish in Journal of Diagnostic Techniques and Biomedical Analysis.
Journal of Diagnostic Techniques and Biomedical Analysis