Mitochondrial ferritin, a new target for inhibiting neuronal tumor cell proliferation

Zhen Hua Shi, Fang Fang Shi, Yue Qi Wang, Alex D. Sheftel, Guangjun Nie, Ya Shuo Zhao, Lin Hao You, Yu Jing Gou, Xiang Lin Duan, Bao Lu Zhao, Hong Meng Xu, Chun Yan Li, Yan Zhong Chang

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Mitochondrial ferritin (FtMt) has a significant effect on the regulation of cytosolic and mitochondrial iron levels. However, because of the deficiency of iron regulatory elements (IRE) in FtMt's gene sequence, the exact function of FtMt remains unclear. In the present study, we found that FtMt dramatically inhibited SH-SY5Y cell proliferation and tumor growth in nude mice. Interestingly, excess FtMt did not adversely affect the development of drosophila. Additionally, we found that the expression of FtMt in human normal brain tissue was significantly higher than that of neuroblastoma, but not higher than that of neurospongioma. However, the expression of transferrin receptor 1 is completely opposite. We therefore hypothesized that increased expression of FtMt may negatively affect the vitality of neuronal tumor cells. Therefore, we further investigated the underlying mechanisms of FtMt's inhibitory effects on neuronal tumor cell proliferation. As expected, FtMt overexpression disturbed the iron homeostasis of tumor cells and significantly downregulated the expression of proliferating cell nuclear antigen. Moreover, FtMt affected cell cycle, causing G1/S arrest by modifying the expression of cyclinD1, cyclinE, Cdk2, Cdk4 and p21. Remarkably, FtMt strongly upregulated the expression of the tumor suppressors, p53 and N-myc downstream-regulated gene-1 (NDRG1), but dramatically decreased C-myc, N-myc and p-Rb levels. This study demonstrates for the first time a new role and mechanism for FtMt in the regulation of cell cycle. We thus propose FtMt as a new candidate target for inhibiting neuronal tumor cell proliferation. Appropriate regulation of FtMt expression may prevent tumor cell growth. Our study may provide a new strategy for neuronal cancer therapy.

Original languageEnglish (US)
Pages (from-to)983-997
Number of pages15
JournalCellular and Molecular Life Sciences
Issue number5
StatePublished - Mar 1 2015


  • Cell cycle
  • Cyclin
  • Cyclin-dependent protein kinase
  • Iron metabolism
  • Neuroblastoma

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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