Two-In-One; Endoplasmic Reticulum and Oxidative Stress Sensor/Response Protein

Too much of unfolded proteins that overwhelms the Endoplasmic reticulum(ER)-coping mechanisms, through over-activity of the Endoplasmic reticulum, or otherwise, will switch the cell from its anti-oxidation pathways over to the unfolded protein stress response(UPR), by putting a halt to protein translation, engaging the degradation of misfolded  proteins and activation of the heat shock protein(hsp)--the chaperone--that folds unfolded proteins. When UPR is prolonged and overwhelmed, apoptosis takes place as ROS, in turn, overwhelm any anti-oxidation-induction. This is characteristic of Alzheimer's, Parkinson's disease and Huntington's disease.

In the trained athlete, the switch to slow-oxidative, fast, fatigue-resistant fibers, lowers ROS levels, which still remain at an anti-oxidation-inducing levels that at the same time promote UPR. This is an adaptation that prepares the muscles for eventual stress.

In the outer membrane of the ER, is a protein that stands guard over ER and makes the organelle take corrective measures to properly fold unfolded or degrade misfolded proteins. This same protein also senses, by binding, molecular oxygen, which molecular oxygen will have derived from reactive oxygen species(ROS). When oxidative stress occurs, combining of IRE-1with molecular oxygen sends signals to anti-oxidation pathways, while UPR is temporarily being halted.

Taken together, this sensor of protein folding, IRE-1, is also a reactive oxygen species(ROS) sensor.

Dr. Oliver Verbe Birnso, MD.

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