RRC ID 57618
Author Nagata R, Nakamura M, Sanaki Y, Igaki T.
Title Cell Competition Is Driven by Autophagy.
Journal Dev Cell
Abstract Cell competition is a quality control process that selectively eliminates unfit cells from the growing tissue via cell-cell interaction. Despite extensive mechanistic studies, the mechanism by which cell elimination is triggered has been elusive. Here, through a genetic screen in Drosophila, we discover that V-ATPase, an essential factor for autophagy, is required for triggering cell competition. Strikingly, autophagy is specifically elevated in prospective "loser" cells nearby wild-type "winner" cells, and blocking autophagy in loser cells abolishes their elimination. Mechanistically, elevated autophagy upregulates a proapoptotic gene hid through NFκB, and the elevated hid cooperates with JNK signaling to effectively induce loser's death. Crucially, this mechanism generally applies to cell competition caused by differences in protein synthesis between cells. Our findings establish a common mechanism of cell competition whereby cells with higher protein synthesis induce autophagy in their neighboring cells, leading to elimination of unfit cells.
Volume 51(1)
Pages 99-112.e4
Published 2019-10-7
DOI 10.1016/j.devcel.2019.08.018
PII S1534-5807(19)30701-4
PMID 31543447
MeSH Animals Apoptosis Autophagy* Binding, Competitive Cell Communication Cell Death Cell Proliferation Drosophila Proteins / metabolism Drosophila melanogaster / genetics* Female Genotype MAP Kinase Kinase 4 / metabolism* Male Mutation NF-kappa B / metabolism* RNA Interference Signal Transduction Transcriptional Activation Up-Regulation
IF 9.19
Times Cited 7
Drosophila 7679R-3 11165R-1 HMS00171 HMJ22258 7486R-1 6794R-1