Figure 1.

Exosomes form through the cellular uptake of extracellular components via endocytosis and plasma membrane invagination. This process initiates the creation of early-sorting endosomes (ESEs) that may bud independently or fuse with preformed ESEs from the ER, TGN, or mitochondria. Fusion with the ER and TGN allows endocytic cargo access to ESEs, progressing to the formation of late-sorting endosomes (LSEs). LSEs undergo invagination, generating intraluminal vesicles (ILVs) that include diverse constituents from various sources. ILVs of different sizes and content result based on invagination volume. LSEs evolve into multivesicular bodies (MVBs), representing future exosomes. MVBs can fuse with autophagosomes for lysosomal degradation or directly fuse with lysosomes. Alternatively, MVBs can travel to the plasma membrane via the cell’s cytoskeleton, docking with MVB-docking proteins on the luminal side. This leads to exocytosis, releasing exosomes with a lipid bilayer orientation akin to the plasma membrane, contributing to the extracellular vesicle pool. Figure is used with permission from the Barrow Neurological Institute, Phoenix, Arizona, USA.