Ferroptosis, a new form of cell death defined after radiation exposure

Abstract

Purpose

Ferroptosis is an iron-dependent form of regulated cell death, driven by excessive lipid peroxidation and/or inactivation/depletion of protective molecules against lipid peroxidation. Ionizing radiation can induce ferroptosis in both normal tissues and tumor cells. Here, we reviewed the findings of ionizing radiation-induced ferroptosis.

Conclusions

Ionizing radiation induces an increase in hydroxyl radicals, free iron, and lipid metabolic enzymes, which subsequently synergistically initiate a high level of lipid peroxidation, making ionizing radiation an exogenous inducer of ferroptosis. In addition, ferroptosis may be the primary form of cell death in the bone marrow under hematopoietic acute radiation syndrome. Ionizing radiation can also induce changes in iron metabolism, which may be a target for regulating ferroptosis. Finally, ionizing radiation-induced ferroptosis initiates from the cytoplasm and ends on the membrane, and is independent of DNA damage.

Keywords:

• Ionizing radiation
• ferroptosis
• iron
• iron metabolism
• phospholipid peroxidation

Disclosure statement

The authors report no conflicts of interest.

Additional information

Funding

This work was supported by the Fundamental Research Funds for the Central Universities [Numbers NS2020042 and NJ2020017-2]; the Postdoctoral Science Foundation of China [Number 2017M611660]; the State Key Laboratory of Bioelectronics-Zhongda Hospital Cross Innovation Cooperation Research Fund [Number 2018yy-jccx012]; the Research Project of Nanjing Shengxun Medical Device Co., Ltd. [Number 2019010027]; the Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions; and the Priority Academic Program Development of Jiangsu Higher Education Institutions. This work was also supported by The Research Project of Nanjing Shengxun Medical Device Co. Ltd.

Notes on contributors

Xiaohong Zhang

Xiaohong Zhang, PhD, is a senior experimentalist at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Xin Li

Xin Li, MS, is a postgraduate at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Chunyan Zheng

Chunyan Zheng, MS, is a postgraduate at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Chunzhi Yang

Chunzhi Yang, is a bachelor of the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Rui Zhang

Rui Zhang, MD, is a chief physician at the Department of Ophthalmology, Zhongda Hospital, Southeast University, Nanjing, PR China.

Ailian Wang

Ailian Wang, MD, is a chief physician at the Department of Ophthalmology, the First Affiliated Hospital, Bengbu Medical College, Bengbu, PR China.

Jundong Feng

Jundong Feng, PhD, is an associate professor at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Xiaodan Hu

Xiaodan Hu, PhD, is an associate professor at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Shuquan Chang

Shuquan Chang, PhD, is the head of the Department at Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.

Haiqian Zhang

Haiqian Zhang, PhD, is a professor at the Department of Nuclear Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, PR China.