Heat Stress Triggers Nuclear Invagination and Spatial Compartmentalization of Protein Metabolism

Heat stress is a common challenge for cells, causing multiple types of cellular damage while triggering complex stress responses, including the highly conserved mechanism known as the heat shock response (HSR). However, the subcellular coordination of these stress responses remains poorly understood. In this study, we identify reversible nuclear morphological changes under heat stress, characterised by kidney-shaped invaginations. These nuclear invaginations are associated with intermediate filament collapse and the regional clustering of organelles. Through immunofluorescence imaging and proteomic analysis, we further reveal that nuclear invagination regions function as specialised compartments where newly synthesised proteins are concentrated and protein degradation demand is heightened. Moreover, this compartmentalization is not only essential for cellular adaptation and recovery from heat stress but also correlates with the differential heat tolerance across cell lines. Our findings highlight a previously unappreciated mechanism by which cells spatially reorganise protein metabolism to optimise stress responses, providing new insights into cellular stress adaptation.