Drosophila p53 integrates the antagonism between autophagy and apoptosis in response to stress. Issue 5 (4th May 2019)

• Record Type: Journal Article
• Authors: Robin, Marion; Issa, Abdul Raouf; Santos, Cristiana C.; Napoletano, Francesco; Petitgas, Céline; Chatelain, Gilles; Ruby, Mathilde; Walter, Ludivine; Birman, Serge; Domingos, Pedro M.; Calvi, Brian R.; Mollereau, Bertrand
• Is Part Of: Autophagy. Volume 15:Issue 5(2019)
• Page Start: 771
• Page End: 784
• Publication Date: 2019-05-04
• Subjects: Apoptosis -- caspase -- Drosophila melanogaster -- macroautophagy -- neurodegenerative disease -- oxidative stress -- p53 -- Parkinson disease -- photoreceptor; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2018.1558001
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: The tumor suppressor TP53/p53 is a known regulator of apoptosis and macroautophagy/autophagy. However, the molecular mechanism by which TP53 regulates 2 apparently incompatible processes remains unknown. We found that Drosophila lacking p53 displayed impaired autophagic flux, higher caspase activation and mortality in response to oxidative stress compared with wild-type flies. Moreover, autophagy and apoptosis were differentially regulated by the p53 (p53B) and ΔNp53 (p53A) isoforms: while the former induced autophagy in differentiated neurons, which protected against cell death, the latter inhibited autophagy by activating the caspases Dronc, Drice, and Dcp-1. Our results demonstrate that the differential use of p53 isoforms combined with the antagonism between apoptosis and autophagy ensures the generation of an appropriate p53 biological response to stress.