Regulation of cell-non-autonomous proteostasis in metazoans

Cells have developed robust adaptation mechanisms to survive environmental conditions that challenge the integrity of their proteome and ensure cellular viability. These are stress signalling pathways that integrate extracellular signals with the ability to detect and efficiently respond to protein-folding perturbations within the cell. Within the context of an organism, the cell-autonomous effects of these signalling mechanisms are superimposed by cell-non-autonomous stress signalling pathways that allow co-ordination of stress responses across tissues. These transcellular stress signalling pathways orchestrate and maintain the cellular proteome at an organismal level. This article focuses on mechanisms in both invertebrate and vertebrate organisms that activate stress responses in a cell-non-autonomous manner. We discuss emerging insights and provide specific examples on how components of the cell-non-autonomous proteostasis network are used in cancer and protein-folding diseases to drive disease progression across tissues.