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 classical heat shock response. However, the subcellular coordination of these stress responses remains poorly understood. In this study, we identify reversible nuclear morphological changes under heat stress, characterized 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 region function as "protein metabolism hotspots", where both protein translation and degradation are enhanced. 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 reorganize protein metabolism to optimize stress responses, providing new insights into heat stress adaptation.