Cell Competition Triggers Suicide by Autophagy

Abstract

Cell competition eradicates weaker cells from an epithelium and is important for organ homeostasis. In this issue of Developmental Cell, Nagata et al. (2019) uncover that eradication of loser cells depends on autophagy-mediated cell death.Originally defined in Drosophila, cell competition entails recognition of relative fitness levels and elimination of the less fit loser cells by winner cells (Morata and Ripoll, 1975). Relative fitness decline like that observed upon loss of one copy of ribosomal components (Minute/+) or relative low levels of Myc, a stimulator of ribosomal biogenesis and protein translation, triggers loser-cell elimination. Cell competition can also be instilled by transformed tumor cells upon expression of Myc, Yorkie (YAP), Wnt/Wg, or JAK-STAT activity that endows these cells the power as ''super competitors'' over normal neighbors (Amoyel and Bach, 2014).Using a clever strategy, in this issue of Developmental Cell Igaki and colleagues (Nagata et al., 2019) devised a genetic screen to define new cell competition components based on the salient features of cell competition-losing when facing wild-type cells but surviving when without wild-type competition.One such ''hit'' identified the gene Helicase at 25E (Hel25E) encoding a RNA helicase implicated in mRNA splicing and mRNA transport out of the nucleus. As predicted, Hel25E À/À mutant cells display reduced protein production compared to wild-type neighbors. Thus, Hel25E À/À mutant cells appear to conform to related loser-cell situations seen in Myc low or Minute/+ cells that also suffer lower protein production. Indeed, like Myc low and RpL14 +/À (Minute) clones, Hel25E À/À loser-cell death occurs specifically at the immediate interface with winner cells, and blocking Caspase activity partially rescued loser-cell elimination. Thus, Hel25E À/À cells obey both context and spatial rules of apoptotic cell elimination typical of cell competition.