abstract
- Autophagy has emerged as a potential drug target for enhancing the efficacy of radiotherapy but its precise role in cellular responses to ionizing radiation (IR) remains incompletely understood. To address this, we conducted a focused RNA interference (RNAi) screen in Drosophila melanogaster targeting autophagy-related genes. We found that knocking down Pink1 or ref(2)P (Drosophila p62/SQSTM1) in larval eye discs resulted in adult eye defects when the larvae were irradiated during the 3rd instar stage. Cell biological analyses revealed that Pink1RNAi expression did not affect cell proliferation or DNA damage recognition/repair but significantly increased apoptosis following IR exposure. This finding was confirmed using loss-of-function mutants of Pink1 and its partner Parkin and was found to extend to larval wing discs. Increased apoptosis after Pink1 depletion was notably concentrated in the G1-arrested morphogenetic furrow (MF). However, Pink1 mutation does not affect G1 arrest in the MF or induction of reactive oxygen species (ROS) by IR, suggesting that the role of Pink1 in protecting cells from IR-induced apoptosis is not via cell cycle regulation or ROS induction. To our knowledge, this is the first report of a role for Pink1/Park in regulating IR-induced apoptosis in any system.