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Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses

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Abstract

Ferritin, an iron-storage protein, regulates cellular iron metabolism and oxidative stress. The ferritin structure is characterized as a spherical cage, inside which large amounts of iron are deposited in a safe, compact and bioavailable form. All ferritins readily catalyze Fe(II) oxidation by peroxides at the ferroxidase center to prevent free Fe(II) from participating in oxygen free radical formation via Fenton chemistry. Thus, ferritin is generally recognized as a cytoprotective stratagem against intracellular oxidative damage The expression of cytosolic ferritins is usually regulated by iron status and oxidative stress at both the transcriptional and post-transcriptional levels. The mechanism of ferritin-mediated iron recycling is far from clarified, though nuclear receptor co-activator 4 (NCOA4) was recently identified as a cargo receptor for ferritin-based lysosomal degradation. Cytosolic ferritins are heteropolymers assembled by H- and L-chains in different proportions. The mitochondrial ferritins are homopolymers and distributed in restricted tissues. They play protective roles in mitochondria where heme- and Fe/S-enzymes are synthesized and high levels of ROS are produced. Genetic ferritin disorders are mainly related to the L-chain mutations, which generally cause severe movement diseases. This review is focused on the biochemistry and function of mammalian intracellular ferritin as the major iron-storage and anti-oxidation protein.

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Acknowledgements

This work was supported by Sanming Project of Medicine in Shenzhen (SZSM201612031), the National Natural Science Foundation of China (81722024, 81772736, 81571728), Chinese Academy of Sciences (YJKYYQ20180048), the Basic Research Foundation for Shenzhen’s Science and Technology (20190726095103499), the National Key Research and Development Program of China (2017YFA0205501, 2017YFA0205503), and the Youth Innovation Promotion Association (2014078).

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  1. Guangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China

    Jianlin Zhang

  2. Institute of Post-transcriptional Medicine, Shenzhen Second People’s Hospital, The First Affiliation Hospital of Shenzhen University, Health Science Center, Shenzhen, 518035, China

    Jianlin Zhang, Aifa Tang, Yang Liu, Ni Xie & Guohui Nie

  3. CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

    Xuehui Chen & Xiyun Yan

  4. Experimental Center of Advanced Materials, School of Materials Science & Engineering, Beijing Institute of Technology, Beijing, 100081, China

    Juanji Hong & Minmin Liang

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Zhang, J., Chen, X., Hong, J. et al. Biochemistry of mammalian ferritins in the regulation of cellular iron homeostasis and oxidative responses. Sci. China Life Sci. 64, 352–362 (2021). https://doi.org/10.1007/s11427-020-1795-4

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