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Lemmer, I.L. ; Willemsen, N.* ; Hilal, N.* ; Bartelt, A.

A guide to understanding endoplasmic reticulum stress in metabolic disorders.

Mol. Metab. 47:101169 (2021)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: The global rise of metabolic disorders, such as obesity, diabetes type 2 and cardiovascular disease, demands a thorough molecular understanding of the cellular mechanisms that govern health or disease. The endoplasmic reticulum (ER) is a key organelle for cellular function and metabolic adaptation and, therefore, disturbed ER function, "ER stress", is a key feature of metabolic disorders. SCOPE OF REVIEW: As ER stress remains an ill-defined phenomenon, this review provides a general guide to understanding the nature, aetiology and consequences of ER stress in metabolic disorders. We define ER stress by its type of stressor, which is driven by proteotoxicity, lipotoxicity, and/or glucotoxicity. We discuss the implications of ER stress in metabolic disorders by reviewing evidence implicating ER phenotypes and organelle communication, protein quality control, calcium homeostasis, lipid and carbohydrate metabolism, and inflammation as key mechanisms in the development of ER stress and metabolic dysfunction. MAJOR CONCLUSIONS: In mammalian biology, ER is a phenotypically and functionally diverse platform for nutrient sensing, which is critical for cell-type specific metabolic control by e.g. hepatocytes, adipocytes, muscle cells, and neurons. In these cells, ER stress is a distinct, transient state of functional imbalance, which is usually resolved by the activation of adaptive programs such as the unfolded protein response (UPR), ER-associated protein degradation (ERAD), or autophagy. However, challenges to proteostasis also impact lipid and glucose metabolism and vice versa. In the ER, both sensing and adaptive measures are integrated and failure of the ER to adapt leads to aberrant metabolism, organelle dysfunction, insulin resistance, and inflammation. In conclusion, the ER is intricately linked to a wide spectrum of cellular functions and is a critical component in maintaining and restoring metabolic health.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Erad ; Nfe2l1 ; Obesity ; Upr ; Ups ; Autophagy ; Calcium Homeostasis ; Diabetes ; Endoplasmic Reticulum ; Glucotoxicity ; Inflammation ; Lipid Metabolism ; Lipotoxicity ; Proteostasis ; Proteotoxicity
ISSN (print) / ISBN 2212-8778
e-ISSN 2212-8778
Zeitschrift Molecular Metabolism
Quellenangaben Band: 47, Heft: , Seiten: , Artikelnummer: 101169 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam
Begutachtungsstatus Peer reviewed
Förderungen Deutsche Forschungsgemeinschaft