PARP-1 is involved in autophagy induced by DNA damage Muñoz-Gámez, José Antonio Rodríguez-Vargas, José Manuel Quiles-Pérez, Rosa Aguilar-Quesada, Rocío MArtín-Oliva, David de Murcia, Gilbert Menissier de Murcia, Josiane Almendros, Antonio Ruiz de Almodóvar, Mariano Oliver, F Javier Oliver, F Javier Autophagy DNA damage PARP-1 Energy Depletion Beclin 1 ATG-5 mTOR Doxorubicin Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. PARP-1 has been implicated in different pathways leading to cell death and its inhibition potentiates chemotherapy-induced cell death. Whether PARP-1 participates in the cell’s decision to commit to autophagy following DNA damage is still not known. To address this issue PARP-1 wild type and deficient cells have been treated with a dose of doxorubicin that induces autophagy. Electron microscopy examination and GFP-LC3 transfection revealed autophagic vesicles and increased expression of genes involved in autophagy (bnip-3, cathepsin b and l and beclin-1) in wild type cells treated with doxo but not in parp-1-/- cells or cells treated with a PARP inhibitor. Mechanistically the lack of autophagic features in PARP-1 deficient/PARP inhibited cells is attributed to prevention of ATP and NAD+ depletion and to the activation of the key autophagy regulator mTOR. Pharmacological or genetical inhibition of autophagy results in increased cell death, suggesting a protective role of autophagy induced by doxorubicin. These results suggest that autophagy might be cytoprotective during the response to DNA damage and suggest that PARP-1 activation is involved in the cell’s decision to undergo autophagy. 2026-02-03T11:49:33Z 2026-02-03T11:49:33Z 2009-01-01 journal article https://hdl.handle.net/10481/110620 https://doi.org/10.4161/auto.5.1.7272 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Landes BioSciences