p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis
PLoS Genet. 2017-09-25; 13(9): e1007024
DOI: 10.1371/journal.pgen.1007024
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Napoletano F(1), Gibert B(2), Yacobi-Sharon K(3), Vincent S(1), Favrot C(2), Mehlen P(2), Girard V(1), Teil M(1), Chatelain G(1), Walter L(1), Arama E(3), Mollereau B(1).
Author information:
(1)Laboratory of Biology and Modelling of the Cell, UMR5239 CNRS/Ecole Normale
Supérieure de Lyon, INSERM U1210, UMS 3444 Biosciences Lyon Gerland, Université
de Lyon, Lyon, France.
(2)Apoptosis, Cancer and Development Laboratory- Equipe labellisée ‘La Ligue’,
LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286,
Université de Lyon, Centre Léon Bérard, Lyon, France.
(3)Department of Molecular Genetics, Weizmann Institute of Science, Rehovot,
Israel.
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.
DOI: 10.1371/journal.pgen.1007024
PMCID: PMC5629030
PMID: 28945745 [Indexed for MEDLINE]
Conflict of interest statement: The authors have declared that no competing
interests exist.