2. Academic Validation
  3. Cytoglobin augments ferroptosis through autophagic degradation of ferritin in colorectal cancer cells

Cytoglobin augments ferroptosis through autophagic degradation of ferritin in colorectal cancer cells

  • Mol Cell Biochem. 2024 Nov 6. doi: 10.1007/s11010-024-05148-0.
Chengjiang Fan # 1,  Ziyang Luo # 1 2,  Qingfang Zheng 1,  Yuhang Xu 1,  Yao Xu 1,  Jianing Chen 1,  You Meng 1,  Haizhong Jiang 3,  Kaitai Liu 4,  Yang Xi 5
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, 315211, China.
  • 2 Institute of Transplantation Medicine, The Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, China.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo, 315000, China.
  • 4 Department of Radiation Oncology, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, 315001, China.
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, 315211, China. xiyang@nbu.edu.cn.
  • # Contributed equally.
PMID: 39503803 DOI: 10.1007/s11010-024-05148-0
Abstract

Autophagy has gained importance in the context of Ferroptosis. Nevertheless, a deeper understanding of the regulatory mechanism governing autophagy-dependent Ferroptosis is necessary. Cytoglobin (CYGB), a member of the globin family, exhibits antifibrotic effects, regulates cellular Reactive Oxygen Species, and stimulates tumor inhibition. Herein, we present further insights into the role of CYGB in Ferroptosis regulation. Our investigation confirmed that CYGB impedes cell proliferation and migration. Furthermore, a significant association between CYGB and the lysosomal pathway was suggested based on the RNA Sequencing data analysis. Elevated lysosomal signal and colocalization of CYGB with lysosome-associated membrane glycoprotein 1 (LAMP1) were observed. Moreover, upregulated Autophagy and augmented Ferroptosis induced by RSL3 were confirmed in CYGB-overexpression cells with an obviously increased colocalization of nuclear receptor coactivator 4 (NCOA4) and LC3B. The Autophagy Inhibitor bafilomycin or chloroquine alleviated autophagy-dependent degradation of ferritin protein under RSL3 treated condition. Additionally, a colocalization of CYGB with the Transferrin Receptor (TFR) was confirmed. Our results demonstrate an important functional pathway by which CYGB regulates Ferroptosis through TFR-binding and autophagic degradation of ferritin, and provide a potential pathway for the treatment of colorectal Cancer.

Keywords

Colorectal cancer; Cytoglobin; Ferritin; Ferroptosis.

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