A new study by Janelia researchers details how nutrient-starved cells divert protein transport stations to cellular recycling centers to be broken down, highlighting a novel approach cells use to deal with stressful conditions.

New proteins bound for outside the cell are manufactured on the endoplasmic reticulum (ER) – a snaking membrane inside the cell. Grape-like tubular outgrowths on the ER called ER exit sites serve as transport stations, collecting these newly synthesized proteins and delivering them to the next step in their journey.

In recent years, scientists have discovered that these ER exit sites also help deliver cellular material and misfolded proteins to lysosomes -- organelles that degrade and recycle material in the cell -- and provide a platform for replication of viruses, including COVID-19. But researchers were perplexed how this one structure, the ER exit site, can participate in all these diverse functions.

In a new study, researchers led by Ya-Cheng Liao, a former postdoc in the Lippincott-Schwartz lab and now an assistant professor at Columbia University, used super-resolution live cell imaging and volume electron microscopy to examine the effect of nutrient stress on ER exit sites.

The team found that the stress triggers a series of molecules to work together to direct ER exit sites to lysosomes where they are destroyed – a novel pathway the cell may use to free up amino acids needed to make proteins inside the cell.

This video shows enhanced FIB-SEM images of cells treated with Torin, which causes nutrient stress. The ER exit sites (magenta), budding off the ER (blue), are in close proximity to the lysosome-related structure (cyan). In some cases, the ER exit sites are in the process of being engulfed by the lysosome.

Credit: Liao et al.