Role of the unfolded protein response in organ physiology: lessons from mouse models.
The endoplasmic reticulum (ER) is a key subcellular compartment involved in the folding and maturation of around one-third of the total proteome. Accumulation of misfolded proteins in the ER lumen engages a signal transduction pathway known as unfolded protein response (UPR) that feedback to recover ER homeostasis or to trigger apoptosis of irreversible damaged cells. The UPR is initiated by three main stress sensors including protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6), and inositol-requiring protein 1α (IRE1α), which reprogram the genome through the control of downstream transcription factors. In this article, the authors have reviewed most relevant studies uncovering the physiological function of the UPR in different organs and tissues based on the phenotypes observed after genetic manipulation of the pathway in vivo. Biomedical applications of targeting the UPR on a disease context are also discussed.
Biomedical Neuroscience Institute, Faculty of Medicine, University of Chile, Santiago, Chile; Center for Molecular Studies of the Cell, Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, University of Chile, Santiago, Chile.
Víctor Hugo
VH
Cornejo
Philippe
P
Pihán
René Luis
RL
Vidal
Claudio
C
Hetz
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D051379:Mice; D009928:Organ Specificity; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D056811:Unfolded Protein Response; D019892:eIF-2 Kinase / Q000378:metabolism
D014157:Transcription Factors; D019892:eIF-2 Kinase
ER stress; mouse model; protein misfolding; secretory cells; unfolded protein response