Mitochondrial Dysfunction Predisposes Radioresistant Insect Cells to Ionizing Radiation by Impairing DNA Repair.

Area of Science:

• Cell Biology
• Radiation Biology
• Mitochondrial Biology

Background:

• Insect cell lines like Spodoptera frugiperda Sf9 are models for studying ionizing radiation (IR) responses.
• Mitochondria play a key role in cellular responses to IR, influencing reactive oxygen species (ROS) production and apoptosis.
• Understanding mitochondrial contributions to intrinsic radioresistance is crucial for lepidopteran insect cells.

Purpose of the Study:

• To compare the radiation responses of parental Sf9 cells and a mitochondrial dysfunction variant (Sf9N).
• To elucidate the specific contribution of mitochondria to the radioresistance of lepidopteran insect cells.
• To investigate the role of the mitochondrial permeability transition pore (mPTP) in radiation-induced cytotoxicity.

Main Methods:

• Exposure of Sf9 and Sf9N cells to gamma radiation (1000 and 2000 Gy).
• Assessment of apoptosis, oxidative stress, mitochondrial membrane potential (MMP), cardiolipin oxidation, and DNA damage/repair kinetics.
• Evaluation of the effect of cyclosporin A (CsA), an mPTP inhibitor, on cell viability and MMP post-irradiation.

Main Results:

• Sf9N cells showed increased radiosensitivity with greater MMP collapse and cardiolipin oxidation compared to Sf9 cells.
• Sf9N cells exhibited enhanced apoptosis and persistent DNA damage, while Sf9 cells demonstrated more efficient DNA repair.
• CsA treatment preserved MMP integrity and improved Sf9N cell viability, indicating mPTP opening mediates IR-induced cytotoxicity.

Conclusions:

• Mitochondrial dysfunction increases radiosensitivity in insect cells.
• Mitochondrial permeability transition pore (mPTP) opening is a critical factor in radiation-induced cell death.
• Mitochondrial regulation plays a key role in determining cellular radiosensitivity to ionizing radiation.