Membraneless organelles, typically formed through phase separation, compartmentalise cellular functions and enable rapid responses to environmental changes. Here (Jennrich et al., 2025), Katherine Bohnsack and colleagues characterise a new type of membraneless organelle in Saccharomyces cerevisiae, enriched with components of the guided entry of tail-anchored proteins (GET) targeting pathway, which directs proteins to the endoplasmic reticulum. The authors show that GET bodies form upon glucose withdrawal and contain the pre-targeting complex components Sgt2, Get3, Get4 and Get5, with Sgt2 acting as a scaffold for GET body formation via its tetratricopeptide repeat region. Mass spectrometry and high-throughput microscopy reveal that GET bodies are enriched in Hsp70 family chaperones and metabolic enzymes. The co-chaperones Sis1 and Sti1 were identified as nucleating factors for GET bodies, indicating a hierarchical assembly pathway. Interestingly, unlike protein aggregates, GET bodies are dynamic, rapidly dissolving upon glucose re-addition or NADH exposure, suggesting their disassembly is metabolically regulated through changes in the cellular redox state. This indicates they might function to sequester or rapidly deploy energy-consuming factors depending on nutrient availability. Together, these findings expand our understanding of phase-separated compartments and provide new insights into how cells reorganise molecular machineries under stress and adapt to nutrient fluctuations.
