Cell competition is a conserved fitness quality control that eliminates cells that are less-fit than
their neighbours. How winner cells induce the elimination of losers is poorly understood. We tackle
this question by studying the onset of differentiation in mice, where cell competition eliminates 35%
of embryonic cells. These loser cells have mitochondrial dysfunction, which we show causes amino
acid deprivation and activation of the integrated stress response (ISR), a pathway essential for
their survival. We demonstrate that L-Proline is a key amino acid sensed by the ISR and that, in a
Proline, that represses the ISR and drives their elimination. These results indicate that cell
competition acts as a novel tissue sparing mechanism, regulated by the availability of extracellular
amino acids, that allows for the elimination of dysfunctional cells when amino acids are plentiful
but ensures their survival in nutrient-poor environments.