Hemochromatosis: as a conformational disorder.
Hereditary hemochromatosis (HH) refers to a unique clinicopathologic subset of iron overload syndromes that includes the disorder related to C282Y homozygous mutation of the hemochromatosis protein (HFE), the most common form of hereditary hemochromatosis. Recent reports have highlighted analogies with the class of disorders, known as the conformational diseases whereby HFE C282Y mutant protein forms aggregates and is subsequently retained in the endoplasmic reticulum (ER). In conformational disorders, accumulation of unfolded or misfolded proteins in the ER can activate a complex cascade linked to the regulation of diverse physiologic processes, disease onset and progression. To-date, reviews on HFE C282Y HH have largely dealt with the end-stage consequence of this disorder (iron overload). However, our review focuses on upstream molecular events resulting from the mislocalization of the aggregation-prone HFE C282Y protein leading to potential advances in treatment and diagnosis.
Translational Cancer Research Group, Department of Clinical Medicine, Institute of Molecular Medicine, Trinity Centre for Health Sciences, St. James's Hospital, Dublin 8, Ireland.
Steven G
SG
Gray
John
J
Crowe
Matthew W
MW
Lawless
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D006432:Hemochromatosis / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins