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Published on: June 3, 2016
NFS1 Plays a Critical Role in Regulating Ferroptosis Homeostasis
Siying Sun1,2, Hanwen Cao1,2, Xuemei Li1,2,3,4,5
1School of Optometry, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
Abstract:
Ferroptosis is an iron-dependent form of regulated cell death (RCD) characterized by intracellular iron homeostasis disruption and lipid peroxide accumulation. It is involved in many pathological processes, including malignant tumors, cardiovascular diseases, inflammatory diseases, and mitochondrial disorders. Cysteine desulfurase (NFS1), a key enzyme in mitochondrial iron-sulfur (Fe-S) cluster biosynthesis, participates in regulating cellular ferroptosis by maintaining Fe-S cluster homeostasis and modulating the ACO1/IRP1 axis, the Xc--glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis, and the p53/STAT signaling pathway. When the function of NFS1 is abnormal, the intracellular free iron level is elevated, followed by reactive oxygen species (ROS) accumulation and lipid peroxidation. NFS1 expression exhibits significant variation across different tissues. Upregulation of NFS1 in tumors can enhance tumor cell resistance to ferroptosis; thus, it can promote tumor growth, drug resistance, and metastatic ability. Conversely, downregulation of NFS1 in cardiomyocytes and neurons exacerbates ferroptosis and causes functional impairment. Here, we systematically review recent advances in the molecular mechanisms of NFS1-mediated ferroptosis and its role in various disease models, intending to clarify key components in the upstream regulatory network of ferroptosis and explore the application value of NFS1 as a potential therapeutic target. The review shows that NFS1 plays an important role in cellular fate regulation, which has significant clinical application potential in the treatment of cancer and interventions for neurological and cardiovascular diseases. Therefore, it can provide a new theoretical basis and research direction for subsequent mechanism research and targeted therapeutic strategy development.
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