Cell competition allows winner cells to eliminate less fit loser cells in tissues. In Minute cell competition, cells with a heterozygous mutation in ribosome genes, such as RpS3^+/− cells, are eliminated by wild-type cells. How cells are primed as losers is partially understood and it has been proposed that reduced translation underpins the loser status of ribosome mutant, or Minute, cells. Here, using Drosophila, we show that reduced translation does not cause cell competition. Instead, we identify proteotoxic stress as the underlying cause of the loser status for Minute competition and competition induced by mahjong, an unrelated loser gene. RpS3^+/− cells exhibit reduced autophagic and proteasomal flux, accumulate protein aggregates and can be rescued from competition by improving their proteostasis. Conversely, inducing proteotoxic stress is sufficient to turn otherwise wild-type cells into losers. Thus, we propose that tissues may preserve their health through a proteostasis-based mechanism of cell competition and cell selection.

细胞竞争使获胜细胞能够消除组织中不太适应的失败细胞。在微小细胞竞争中，核糖体基因杂合突变的细胞（例如RpS3 ^+/-细胞）被野生型细胞淘汰。细胞如何被引导为失败者已被部分了解，并且有人提出翻译减少支撑了核糖体突变体或微小细胞的失败者状态。在这里，使用果蝇，我们证明减少翻译不会引起细胞竞争。相反，我们将蛋白毒性应激确定为分钟竞争和麻将（一种不相关的失败者基因）引起的竞争失败者状态的根本原因。 RpS3 ^+/-细胞表现出自噬和蛋白酶体通量减少，积累蛋白质聚集体，并且可以通过改善其蛋白质稳态来避免竞争。相反，诱导蛋白毒性应激足以将野生型细胞变成失败者。因此，我们认为组织可以通过基于蛋白质稳态的细胞竞争和细胞选择机制来保持健康。