fig1

Figure 1. Biogenesis of extracellular vesicles and the structure and contents of exosomes. The formation of exosomes included four steps: (i) ESEs formation: Through the mechanisms of endocytosis and invagination of the plasma membrane, ESEs are formed, a process energized by Mt; (ii) LSE formation: After cytoplasmic sorting, ESEs mature and eventually form LSEs. During the formation of ESEs and LSEs, they are capable of exchanging materials with the cell nucleus, ER, and GA; (iii) MVB formation: LSEs’ membrane buds inwardly to form multiple ILVs (future exosomes), which eventually transform into MVBs; (iv) Release: MVBs fuse with the plasma membrane, and ILVs released to extracellular space are called exosomes. Ectosomes are vesicles that pinch off the surface of the plasma membrane via outward budding. Exosomes have a diameter of 30-150 nm and a bilayer membrane structure, while ectosomes range from 50 to 1 mm in diameter. EVs are highly heterogeneous bilayer membrane structures carrying diverse cargos, such as proteins, nucleic acids, and lipids, and their content can vary significantly across different cells and conditions. ESEs: Early sorting endosomes; Mt: mitochondria; LSEs: late sorting endosomes; MVBs: multivesicular bodies; ILVs: intraluminal vesicles; ER: endoplasmic reticulum; GA: Golgi apparatus; SHH: Sonic Hedgehog; Evs: extracellular vesicles; TGF-β: transforming growth factor beta; IL-6: interleukin-6; TCA: tricarboxylic acid.