Different mitochondrial fragmentation after irradiation with X-rays and carbon ions in HeLa cells and its influence on cellular apoptosis

Xiaodong Jin; Feifei Li; Bingtao Liu; Xiaogang Zheng; Hongbin Li; Fei Ye; Weiqiang Chen; Qiang Li

doi:10.1016/j.bbrc.2018.04.214

Different mitochondrial fragmentation after irradiation with X-rays and carbon ions in HeLa cells and its influence on cellular apoptosis

Biochem Biophys Res Commun. 2018 Jun 12;500(4):958-965. doi: 10.1016/j.bbrc.2018.04.214. Epub 2018 May 2.

Authors

Xiaodong Jin¹, Feifei Li², Bingtao Liu², Xiaogang Zheng¹, Hongbin Li², Fei Ye¹, Weiqiang Chen¹, Qiang Li³

Affiliations

¹ Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 730000, China.
² Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 730000, China; University of Chinese Academy of Sciences, Beijing, 100049, China.
³ Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou, 730000, China; Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou, 730000, China. Electronic address: [email protected].

PMID: 29709476
DOI: 10.1016/j.bbrc.2018.04.214

Abstract

Although mitochondria are known to play an important role in radiation-induced cellular damage, the mechanisms by which ionizing radiation modulates mitochondrial dynamics are largely unknown. In this study, human cervical carcinoma cell line HeLa was used to demonstrate the different modes of mitochondrial network in response to different quality radiations such as low linear energy transfer (LET) X-rays and high-LET carbon ions. Mitochondria fragmented into punctate and clustered ones upon carbon ion irradiation in a dose- and LET-dependent manner, which was associated with apoptotic cell death. In contrast, low-dose X-ray irradiation promoted mitochondrial fusion while mitochondrial fission was detected until the radiation dose was more than 1 Gy. This fission was driven by ERK1/2-mediated phosphorylation of Drp1 on Serine 616. Inhibition of mitochondrial fragmentation suppressed the radiation-induced apoptosis and thus enhanced the resistance of cells to carbon ions and high-dose X-rays, but not for cells irradiated with X-rays at the low dose. Our results suggest that radiations of different qualities cause diverse changes of mitochondrial dynamics in cancer cells, which play an important role in determining the cell fate.

Keywords: Apoptosis; Different quality radiations; Mitochondrial dynamics; Radiosensitivity; Release of cytochrome c.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Apoptosis / genetics
Apoptosis / radiation effects*
Benzamides / pharmacology
Carbon / adverse effects
Diphenylamine / analogs & derivatives
Diphenylamine / pharmacology
Dose-Response Relationship, Radiation
Dynamins
GTP Phosphohydrolases / antagonists & inhibitors
GTP Phosphohydrolases / genetics
GTP Phosphohydrolases / metabolism
Gene Expression Regulation, Neoplastic*
HeLa Cells
Humans
Linear Energy Transfer
Microtubule-Associated Proteins / antagonists & inhibitors
Microtubule-Associated Proteins / genetics
Microtubule-Associated Proteins / metabolism
Mitochondria / drug effects
Mitochondria / metabolism
Mitochondria / radiation effects*
Mitochondria / ultrastructure
Mitochondrial Dynamics / drug effects
Mitochondrial Dynamics / radiation effects*
Mitochondrial Proteins / antagonists & inhibitors
Mitochondrial Proteins / genetics
Mitochondrial Proteins / metabolism
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / genetics
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / genetics
Mitogen-Activated Protein Kinase 3 / metabolism
Protein Kinase Inhibitors / pharmacology
Radiation Tolerance / genetics*
Signal Transduction
X-Rays / adverse effects

Substances

Benzamides
Microtubule-Associated Proteins
Mitochondrial Proteins
Protein Kinase Inhibitors
Carbon
mirdametinib
Diphenylamine
MAPK1 protein, human
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
GTP Phosphohydrolases
DNM1L protein, human
Dynamins