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Journal article

Proteostasis : bad news and good news from the endoplasmic reticulum

  • Noack, Julia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Brambilla Pisoni, Giorgia Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
  • Molinari, Maurizio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Switzerland
    21.08.2014
Published in:
  • Swiss medical weekly. - 2014, vol. 144, p. w14001
Endoplasmic reticulum (ER)
Chemical chaperones
Pharmacologic chaperones
Protein folding
Protein quality control
Proteopathies
Conformational diseases
Proteostasis network
ER associated degradation (ERAD)
Unfolded protein response (UPR)
English The endoplasmic reticulum (ER) is an intracellular compartment dedicated to the synthesis and maturation of secretory and membrane proteins, totalling about 30% of the total eukaryotic cells proteome. The capacity to produce correctly folded polypeptides and to transport them to their correct intra- or extracellular destinations relies on proteostasis networks that regulate and balance the activity of protein folding, quality control, transport and degradation machineries. Nutrient and environmental changes, pathogen infection aging and, more relevant for the topics discussed in this review, mutations that impair attainment of the correct 3D structure of nascent polypeptide chains may compromise the activity of the proteostasis networks with devastating consequences on cells, organs and organisms’ homeostasis. Here we present a review of mechanisms regulating folding and quality control of proteins expressed in the ER, and we describe the protein degradation and the ER stress pathways activated by the expression of misfolded proteins in the ER lumen. Finally, we highlight select examples of proteopathies (also known as conformational disorders or protein misfolding diseases) caused by protein misfolding in the ER and/or affecting cellular proteostasis and therapeutic interventions that might alleviate or cure the disease symptoms.
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  • English
Classification
Chemistry
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https://n2t.net/ark:/12658/srd1319028
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