Fig. 1.

Exosome biogenesis and secretion. Fluid and extracellular constituents such as proteins, lipids, and small molecules can enter cells, along with cell surface proteins, through endocytosis and plasma membrane invagination. Then, the cup-shaped structure enters the de novo formation of an early-sorting endosome (ESE), including processes such as exchanging cargoes with the trans-Golgi network and endoplasmic reticulum and taking in some cargoes from mitochondria or merging with a pre-existing ESE. Next, the ESE turns into a late-sorting endosome (LSE). Then, the late-sorting endosomal membrane is invaginated to generate intraluminal vesicles (ILVs) and to further modify the cargoes of future exosomes with cytoplasmic constituents. After the defined collection of ILVs (future exosomes), LSEs are turned into MVBs. Radiation can cause DNA single-strand breaks (SSBs) and double-strand breaks (DSBs) in tumor cells. After DNA damage, tumor suppressor-activated pathway 6 (TSAP6) is activated. Then the p53 protein is activated to become a transcription factor and involve in the formation of exosomes. MVBs can fuse with autophagosomes, and ultimately the contents can undergo degradation in the lysosomes. MVBs can also be transported to the plasma membrane through the cytoskeletal and microtubule network of the cell and dock on the luminal side of the plasma membrane with the help of MVB-docking proteins. Exocytosis follows and results in the release of the exosomes