RRC ID 57242
Author Napoletano F, Gibert B, Yacobi-Sharon K, Vincent S, Favrot C, Mehlen P, Girard V, Teil M, Chatelain G, Walter L, Arama E, Mollereau B.
Title p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis.
Journal PLoS Genet
Abstract The importance of regulated necrosis in pathologies such as cerebral stroke and myocardial infarction is now fully recognized. However, the physiological relevance of regulated necrosis remains unclear. Here, we report a conserved role for p53 in regulating necrosis in Drosophila and mammalian spermatogenesis. We found that Drosophila p53 is required for the programmed necrosis that occurs spontaneously in mitotic germ cells during spermatogenesis. This form of necrosis involved an atypical function of the initiator caspase Dronc/Caspase 9, independent of its catalytic activity. Prevention of p53-dependent necrosis resulted in testicular hyperplasia, which was reversed by restoring necrosis in spermatogonia. In mouse testes, p53 was required for heat-induced germ cell necrosis, indicating that regulation of necrosis is a primordial function of p53 conserved from invertebrates to vertebrates. Drosophila and mouse spermatogenesis will thus be useful models to identify inducers of necrosis to treat cancers that are refractory to apoptosis.
Volume 13(9)
Pages e1007024
Published 2017-9-1
DOI 10.1371/journal.pgen.1007024
PMID 28945745
PMC PMC5629030
MeSH Animals Apoptosis / genetics Caspase 9 / genetics Caspases / genetics Disease Models, Animal Drosophila Proteins / genetics Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Germ Cells / growth & development Germ Cells / pathology Homeostasis / genetics Humans Hyperplasia / genetics Hyperplasia / pathology Male Mice Necrosis / genetics* Necrosis / pathology Spermatogenesis / genetics* Testis / growth & development Testis / metabolism Tumor Suppressor Protein p53 / genetics*
IF 5.224
Times Cited 16