Lysosomes orchestrate the degradation of macromolecules, are signalling hubs and have an important role in cellular homeostasis. Many factors can induce lysosomal damage, which can be detected by various mechanisms, resulting in lysosome repair, removal or replacement. Lysosomal damage has been reported to induce the formation of stress granules, but the underlying mechanisms are unclear. Duran et al. now describe a calcium-dependent cell survival pathway that induces stress granule formation following lysosomal damage.

Inactivation of mTOR complex 1 (mTORC1) and phosphorylation of the translation initiation factor eIF2α are known to lead to global translation inhibition and stress granule formation. Lysosomal damage induced mTORC1 inhibition and eIF2α phosphorylation, as expected. However, whereas eIF2α depletion suppressed stress granule formation upon lysosomal damage, it did not affect mTORC1 inactivation. Moreover, keeping mTORC1 active following lysosomal damage did not impede the formation of stress granules. Overall, these observations indicate that eIF2α phosphorylation, but not the mTORC1 pathway, is important in the formation of stress granules upon lysosomal damage.