Le stress du réticulum endoplasmique: Adaptation et toxicité

Abstract

The majority of surface and secreted proteins are synthesized in the endoplasmic reticulum where they must acquire the right conformation and assemble before being transported. Under specific cellular conditions, unfolded protein can accumulate and initiate the unfolded protein response (UPR). In mammals, this adaptative response includes transcriptional activation of genes which enhances endoplasmic reticulum folding and endoplasmic reticulum-associated degradation capacities, and translation attenuation to limit further entry of proteins in the endoplasmic reticulum. The intracellular signal transduction cascades are mediated by endoplasmic reticulum transmembrane proteins and involve unconventional mRNA splicing. if this adaptative response is not sufficient, apoptotic death is triggered. The endoplasmic reticulum stress and/or cellular death, sometimes induced during UPR, seem involved in the physiopothology of some disease such as α1-antitrypsine deficiency and AR-JP, a specific form of Parkinson's disease.