Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 10;24(2):1337.
doi: 10.3390/ijms24021337.

The Machinery of Exosomes: Biogenesis, Release, and Uptake

Sofia V Krylova  1   2   3 , Daorong Feng  1   3
Affiliations
Review

The Machinery of Exosomes: Biogenesis, Release, and Uptake

Sofia V Krylova et al. Int J Mol Sci. .

Abstract

Exosomes are a subtype of membrane-contained vesicles 40-200 nm in diameter that are secreted by cells into their surroundings. By transporting proteins, lipids, mRNA, miRNA, lncRNA, and DNA, exosomes are able to perform such vital functions as maintaining cellular homeostasis, removing cellular debris, and facilitating intercellular and interorgan communication. Exosomes travel in all body fluids and deliver their molecular messages in autocrine, paracrine as well as endocrine manners. In recent years, there has been an increased interest in studying exosomes as diagnostic markers and therapeutic targets, since in many disease conditions this machinery becomes dysregulated or hijacked by pathological processes. Additionally, delivery of exosomes and exosomal miRNA has already been shown to improve systemic metabolism and inhibit progression of cancer development in mice. However, the subcellular machinery of exosomes, including their biogenesis, release and uptake, remains largely unknown. This review will bring molecular details of these processes up to date with the goal of expanding the knowledge basis for designing impactful exosome experiments in the future.

Keywords: cargo sorting; exosome biogenesis; exosome secretion; exosome uptake.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of the exosome machinery. Cargos are sorted by endocytosis to the early endosomes. Early endosomes are committed to the endosomal maturation pathway, which results in multivesicular appearance of the late endosomes (MVB). Finally, MVBs fuse with the plasma membrane (PM) to release exosomes. Created with BioRender.com.
Figure 2
Figure 2
Exosome biogenesis. (A) ESCRT-dependent ILVs biogenesis. 1. Classic pathways from ESCRT 0-III-Vps4. 2. ESCRT 0-Bro1/ALIX-ESCRT III. 3. ALIX-ESCRT III. 4. Bro1-Vps4-ESCRT III. (B) ESCRT-independent ILVs biogenesis. Created with BioRender.com.
Figure 3
Figure 3
Cargo sorting into exosomes. The known pathways of protein, RNA, and DNA sorting are depicted. Exosomal membrane proteins including tetraspanins, flotillin, integrins, MHCs, and ESCRT are labeled. Created with BioRender.com.
Figure 4
Figure 4
Exosome secretion. With the help of microtubules, Rabs, and tethering factors, one vesicle SNARE (V-SNARE) forms four-helix bundles with two target SNAREs (T-SNARE) to drive the fusion between MVB with plasma membranes to secret exosomes. Created with BioRender.com.
Figure 5
Figure 5
Exosome uptake. Exosome uptake occurs via one of three pathways: (1) Fusion with the plasma membrane to release exosome contents; (2) Endocytosis; (3) Direct interaction with surface receptors. Created with BioRender.com.
See this image and copyright information in PMC

References

    1. Woodman P.G., Futter C.E. Multivesicular bodies: Co-ordinated progression to maturity. Curr. Opin. Cell Biol. 2008;20:408–414. doi: 10.1016/j.ceb.2008.04.001. - DOI - PMC - PubMed
    1. Grant B.D., Donaldson J.G. Pathways and mechanisms of endocytic recycling. Nat. Rev. Mol. Cell Biol. 2009;10:597–608. doi: 10.1038/nrm2755. - DOI - PMC - PubMed
    1. Megha, London E. Ceramide selectively displaces cholesterol from ordered lipid domains (rafts): Implications for lipid raft structure and function. J. Biol. Chem. 2004;279:9997–10004. doi: 10.1074/jbc.M309992200. - DOI - PubMed
    1. Sonnichsen B., De Renzis S., Nielsen E., Rietdorf J., Zerial M. Distinct membrane domains on endosomes in the recycling pathway visualized by multicolor imaging of Rab4, Rab5, and Rab11. J. Cell Biol. 2000;149:901–914. doi: 10.1083/jcb.149.4.901. - DOI - PMC - PubMed
    1. Thery C., Amigorena S., Raposo G., Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr. Protoc. Cell Biol. 2006;30:3.22.1–3.22.29. doi: 10.1002/0471143030.cb0322s30. - DOI - PubMed

LinkOut - more resources