Role of Mitochondria in Radiation Responses: Epigenetic, Metabolic, and Signaling Impacts

Int J Mol Sci. 2021 Oct 13;22(20):11047. doi: 10.3390/ijms222011047.


Until recently, radiation effects have been considered to be mainly due to nuclear DNA damage and their management by repair mechanisms. However, molecular biology studies reveal that the outcomes of exposures to ionizing radiation (IR) highly depend on activation and regulation through other molecular components of organelles that determine cell survival and proliferation capacities. As typical epigenetic-regulated organelles and central power stations of cells, mitochondria play an important pivotal role in those responses. They direct cellular metabolism, energy supply and homeostasis as well as radiation-induced signaling, cell death, and immunological responses. This review is focused on how energy, dose and quality of IR affect mitochondria-dependent epigenetic and functional control at the cellular and tissue level. Low-dose radiation effects on mitochondria appear to be associated with epigenetic and non-targeted effects involved in genomic instability and adaptive responses, whereas high-dose radiation effects (>1 Gy) concern therapeutic effects of radiation and long-term outcomes involving mitochondria-mediated innate and adaptive immune responses. Both effects depend on radiation quality. For example, the increased efficacy of high linear energy transfer particle radiotherapy, e.g., C-ion radiotherapy, relies on the reduction of anastasis, enhanced mitochondria-mediated apoptosis and immunogenic (antitumor) responses.

Keywords: DNA damage response (DDR); ROS; adaptive response; apoptosis; cancer; carbon ions; carbon-ion radiotherapy (CIRT); epigenetics; genomic instability; high LET particle radiation; hormesis; innate and adaptive immune responses; ionizing radiation; metabolism; mitochondria; non-targeted effects (NTEs); radiation quality; radiotherapy; signaling.

Publication types

  • Review

MeSH terms

  • Epigenesis, Genetic / radiation effects*
  • Epithelial-Mesenchymal Transition / radiation effects
  • Genomic Instability / radiation effects
  • Humans
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Mitochondria / radiation effects
  • Mitochondrial Dynamics / radiation effects
  • Oxidative Stress / radiation effects
  • Radiation, Ionizing*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / radiation effects*


  • Reactive Oxygen Species