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ER Stress and Iron Homeostasis : A New Frontier for the UPR
Joint Authors
Pinto, Jorge P.
de Sousa, Maria
Oliveira, Susana J.
Source
Biochemistry Research International
Issue
Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-12-20
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
The C282Y mutation of HFE accounts for the majority of cases of the iron overload disease Hereditary Hemochromatosis (HH).
The conformational changes introduced by this mutation impair the HFE association with β2-microglobulin (β2m) and the cell surface expression of the protein: with two major consequences.
From a functional perspective, the ability of HFE to bind to transferrin receptors 1 and 2 is lost in the C282Y mutant, thus affecting hepcidin regulation.
Also due to the faulty assembly with β2m, HFE-C282Y molecules remain in the endoplasmic reticulum (ER) as aggregates that undergo proteasomal degradation and activate an Unfolded Protein Response (UPR).
UPR activation, regardless of the ER stress stimuli, was shown to reshape the expression profile of iron-related genes and to decrease MHC-I cell surface expression.
The possibility of a HFE-C282Y-mediated interplay between the UPR and iron homeostasis influencing disease progression and the clinical heterogeneity among C282Y carriers is discussed.
The responsiveness of the ER chaperone calreticulin to both ER and iron-induced oxidative stresses, and its correlation with HH patients’ phenotype, reinforce the interest of dissecting the UPR signaling/iron metabolism crosstalk and points to the potential clinical value of use of pharmacological chaperones in HFE-HH.
American Psychological Association (APA)
Oliveira, Susana J.& de Sousa, Maria& Pinto, Jorge P.. 2010. ER Stress and Iron Homeostasis : A New Frontier for the UPR. Biochemistry Research International،Vol. 2011, no. 2011, pp.1-10.
https://search.emarefa.net/detail/BIM-506286
Modern Language Association (MLA)
Oliveira, Susana J.…[et al.]. ER Stress and Iron Homeostasis : A New Frontier for the UPR. Biochemistry Research International No. 2011 (2011), pp.1-10.
https://search.emarefa.net/detail/BIM-506286
American Medical Association (AMA)
Oliveira, Susana J.& de Sousa, Maria& Pinto, Jorge P.. ER Stress and Iron Homeostasis : A New Frontier for the UPR. Biochemistry Research International. 2010. Vol. 2011, no. 2011, pp.1-10.
https://search.emarefa.net/detail/BIM-506286
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-506286