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Cell death by necrosis is not an accidental process

Publication in PLOS Genetics

Published on : October 4, 2017

Laboratory of Biology and Modelling of the Cell (LBMC)

Drosophila testes visualized by confocal microscopy. Necrotic germ cells are visualized in red (white arrowheads), cell nuclei in blue. © Victor Girard

Cell death allows elimination of supernumerary cells during development or of abnormal cells throughout life. Physiological cell death is tightly regulated to prevent pathologies such as degenerative diseases or cancers, which often occur due to excessive or absent cell death, respectively. Understanding the mechanisms of cell death pathways is thus crucial for fighting various diseases. The best studied form of cell death, apoptosis, has classically been considered the sole form of cell death during development, while other forms of cell death, referred to as necrosis, were considered accidental.

Here, we show that a regulated form of necrosis controls germ cell number during Drosophila spermatogenesis, thus demonstrating that necrosis can play a key role in controlling cell number in physiological conditions. This regulated form of necrosis involves p53, a protein frequently mutated in cancer. Furthermore, we demonstrate that this pathway prevents tissue hyperplasia, a condition that can lead to cancer. We also provide evidence that the same pathway is operational in mammals, as shown in the testes of mice subjected to mild heat stress. These findings, published on Sept 25th, 2017, in PLoS Genetics, expand the possible mechanisms by which cell death could be targeted to treat human pathologies.

An international team

p53-dependent programmed necrosis controls germ cell homeostasis during spermatogenesis. 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. PLoS Genet. 2017 Sep 25;13(9):e1007024. doi: 10.1371/journal.pgen.1007024.

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