Low-Dose Non-Targeted Effects and Mitochondrial Control.

Area of Science:

• Radiation Biology
• Mitochondrial Biology
• Cellular Stress Response

Background:

• Non-targeted effects (NTE) of ionizing radiation (IR), previously considered low-dose phenomena, are now observed at high doses relevant to antitumor radiation therapy.
• IR induces intracellular and extracellular signaling, leading to bystander and abscopal effects.
• Mitochondria are central to cellular stress, producing reactive oxygen species (ROS) and influencing energy metabolism (ATP).

Purpose of the Study:

• To review the prominent role of mitochondria in non-targeted effects (NTE) induced by ionizing radiation (IR).
• To explore how mitochondrial dysfunction and signaling contribute to bystander and abscopal effects.
• To understand the implications of these mitochondrial-driven NTE in cell survival and antitumor radiation therapy (RT).

Main Methods:

• Review of existing literature on ionizing radiation (IR), non-targeted effects (NTE), and mitochondrial function.
• Analysis of intracellular and extracellular signaling pathways involved in IR-induced stress responses.
• Focus on mitochondrial roles in energy production, ROS/NOS generation, and cellular reorganization.

Main Results:

• Ionizing radiation (IR) rapidly perturbs mitochondrial function, increasing energy demands and ROS/NOS production.
• Mitochondrial dysfunction triggers cellular reorganization, including autophagy, mitophagy, and cell cycle arrest.
• IR-induced NTE involve molecular mediators released from irradiated cells, affecting bystander and distant cells, and modulating immune responses.

Conclusions:

• Mitochondria are critical determinants of cell survival and response to antitumor radiation therapy (RT).
• Mitochondrial-driven non-targeted effects (NTE) contribute to phenomena like hormesis, genomic instability, and immune modulation.
• Understanding the role of mitochondria in NTE is crucial for optimizing radiation therapy strategies.