Figure 3.

Biogenesis mechanisms of extracellular vesicles. (A) Exosomes biogenesis is governed by two main molecular mechanisms: the Endosomal Sorting Complex Required for Transport (ESCRT)-dependent and the ESCRT-independent pathways. In the first mechanism, several molecular rearrangements of the ESCRT machinery lead to the curving and scission of the membrane of the late endosome, creating the Intraluminal Vesicles (ILVs). In the second mechanism, the biochemical metabolization of sphingomyelin to ceramide by the enzyme sphingomyelinase 2 induces the formation of the ILV. After these processes, the Multivesicular bodies (MVB) either fuse with the lysosomes, degrading their luminal content, or fuse with the cell’s membrane, releasing the ILVs as exosomes in the extracellular milieu. (B) The biogenesis of microvesicles/ectosomes starts with the gathering of their cargo in the inner leaflet of the plasma membrane in specific regions’ designated lipid rafts (enriched in cholesterol and glycosphingolipids). Then, the cell’s cytoskeleton reorganizes, influenced by Arf6 and RhoA proteins, and the outward budding of the microvesicles starts. The ESCRT-dependent and -independent mechanisms described for exosomes biogenesis also play a role in inducing the curvature of the plasma membrane and scission, resulting in the pinching off of the microvesicles. (C) Apoptotic bodies biogenesis originates from the disassembly of cells undergoing apoptosis, through cytoskeleton rearrangements that cause their blebbing from the dying cell, entrapping organelles and pieces of the degraded nucleus, namely DNA and histones.