Ferroportin Disease Mutations Influence Manganese Accumulation and Cytotoxicity

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2018 Sep 25

PMID 30247984

Citations 18

Authors

Eun-Kyung Choi

Trang-Tiffany Nguyen

Shigeki Iwase

Young Ah Seo

Affiliations

Soon will be listed here.

Abstract

Hemochromatosis is a frequent genetic disorder, characterized by the accumulation of excess iron across tissues. Mutations in the FPN1 gene, encoding a cell surface iron exporter [ferroportin (Fpn)], are responsible for hemochromatosis type 4, also known as ferroportin disease. Recently, Fpn has been implicated in the regulation of manganese (Mn), another essential nutrient required for numerous cellular enzymes. However, the roles of Fpn in Mn regulation remain ill-defined, and the impact of disease mutations on cellular Mn levels is unknown. Here, we provide evidence that Fpn can export Mn from cells into extracellular space. Fpn seems to play protective roles in Mn-induced cellular toxicity and oxidative stress. Finally, disease mutations interfere with the role of Fpn in controlling Mn levels as well as the stability of Fpn. These results define the function of Fpn as an exporter of both iron and Mn and highlight the potential involvement of Mn dysregulation in ferroportin disease.-Choi, E.-K., Nguyen, T.-T., Iwase, S., Seo, Y. A. Ferroportin disease mutations influence manganese accumulation and cytotoxicity.

Citing Articles

Neuronal SLC39A8 deficiency impairs cerebellar development by altering manganese homeostasis.

Choi E, Aring L, Peng Y, Correia A, Lieberman A, Iwase S JCI Insight. 2024; 9(20).

PMID: 39435657 PMC: 11530126. DOI: 10.1172/jci.insight.168440.

Manganese transporter SLC30A10 and iron transporters SLC40A1 and SLC11A2 impact dietary manganese absorption.

Prajapati M, Zhang J, Chong G, Chiu L, Mercadante C, Kowalski H bioRxiv. 2024; .

PMID: 39071439 PMC: 11275741. DOI: 10.1101/2024.07.17.603814.

The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease.

Choi E, Rajendiran T, Soni T, Park J, Aring L, Muraleedharan C Nat Commun. 2024; 15(1):4775.

PMID: 38839750 PMC: 11153611. DOI: 10.1038/s41467-024-49049-8.

Hepatic HIF2 is a key determinant of manganese excess and polycythemia in SLC30A10 deficiency.

Prajapati M, Zhang J, Chiu L, Chong G, Mercadante C, Kowalski H JCI Insight. 2024; 9(10).

PMID: 38652538 PMC: 11141921. DOI: 10.1172/jci.insight.169738.

Signal Transduction Associated with Mn-induced Neurological Dysfunction.

Zheng X, Fang Y, Lin J, Luo J, Li S, Aschner M Biol Trace Elem Res. 2023; 202(9):4158-4169.

PMID: 38155332 DOI: 10.1007/s12011-023-03999-0.

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