Regulators of Iron Homeostasis: New Players in Metabolism, Cell Death, and Disease

By Alexander R Bogdan, M. Miyazawa, Kazunori Hashimoto, Y. Tsuji. TIBS -Trends in Biochemical Sciences. Regular ed, 2015

796 citations recorded by the source corpus.

Iron is necessary for life, but can also cause cell death. Accordingly, cells evolved a robust, tightly regulated suite of genes for maintaining iron homeostasis. Previous mechanistic studies on iron homeostasis have granted insight into the role of iron in human health and disease. We highlight new regulators of iron metabolism, including iron-trafficking proteins [solute carrier family 39, SLC39, also known as ZRT/IRT-like protein, ZIP; and poly-(rC)-binding protein, PCBP] and a cargo receptor (NCOA4) that is crucial for release of ferritin-bound iron. We also discuss emerging roles of iron in apoptosis and a novel iron-dependent cell death pathway termed ‘ferroptosis’, the dysregulation of iron metabolism in human pathologies, and the use of iron chelators in cancer therapy.

Subfields: Hematology, Nutrition and Dietetics, Pulmonary and Respiratory Medicine

View Paper: https://www.semanticscholar.org/paper/0d50fdd83003158b7592b995c38301ed468d9cfa

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In Hematology

1. D. Tang

In Nutrition and Dietetics

1. D. Tang
2. R. Kang
3. Guido Kroemer

In Pulmonary and Respiratory Medicine

1. D. Tang
2. Guido Kroemer
3. R. Kang
4. D. Klionsky
5. Jiao Liu
6. P. Lei
7. Qing-zhang Tuo
8. Xin Chen

Citations in the corpus

• Ferroptosis, a new form of cell death, and its relationships with tumourous diseases (2016, background): “In addition, iron has been found to be closely related to the occurrence and progression of tumours, and disorders of iron metabolism might facilitate tumour growth [9, 10].”
• Ferroptosis: mechanisms and links with diseases (2021, background): “Iron can lead to the dissociation of IRPs from the IRE by binding to IRPs, altered translation of target transcripts.(214) Interesting, IREs are found in the 5’-UTR of amyloid precursor protein (APP) and α-synuclein (α-Syn) transcripts, and iron accumulation can upregulate the levels of α-Syn, APP a”
• Role of pyroptosis in inflammation and cancer (2022, background): “In addition to pyroptosis, iron can trigger several types of cell death, such as ferroptosis, ironinduced necroptosis and apoptosis, all of which are consequences of complex signaling pathways in cells [175, 179].”
• Autophagy-Dependent Ferroptosis: Machinery and Regulation (2020, background): “, resulting from the knockdown of SLC40A1/ferroportin) enhance the sensitivity to ferroptosis (Bogdan et al., 2016; Du et al., 2018; Gao et al., 2016; Geng et al., 2018; Hou et al., 2016; Yang and Stockwell, 2008).”