Crosstalk between exosomes and autophagy: A review of molecular mechanisms and therapies

Abstract

Exosomes are extracellular vesicles that primarily exist in bodily fluids such as blood. Autophagy is an intracellular degradation process, which, along with exosomes, can significantly influence human health and has therefore attracted considerable attention in recent years. Exosomes have been shown to regulate the intracellular autophagic process, which, in turn, affects the circulating exosomes. However, crosstalk between exosomal and autophagic pathways is highly complex, depends primarily on the environment, and varies greatly in different diseases. In addition, studies have demonstrated that exosomes, from specific cell, can mitigate several diseases by regulating autophagy, which can also affect the excessive release of some harmful exosomes. This phenomenon lays a theoretical foundation for the improvement of many diseases. Herein, we review the mechanisms and clinical significance of the association and regulation of exosomes and autophagy, in order to provide a new perspective for the prevention and treatment of associated diseases.

Keywords: autophagy; exosomes; mesenchymal stem cells; miRNA; molecular mechanisms; therapies.

FIGURE 1

Components of exosomes and trafficking. Exosomes are secreted into the extracellular space by donor cells and have commonly conserved components, including CD9, CD63, CD81, Alix, flotillin, TSG101, MHC, HSP70, HSP90 and CD47. Exosomes can carry various cargos and interact with recipient cells primarily via three pathways: (1) phagocytosis, (2) ligand‐receptor binding and (3) membrane fusion. Following uptake by recipient cells, exosomes release their cargo, which can modulate autophagy

FIGURE 2

Schematic diagram of the molecular mechanism of autophagy. The autophagic process includes five primary stages, namely initiation, nucleation, elongation and maturation, fusion and degradation. The molecular pathway, comprising the core autophagy proteins, is illustrated. PE, phosphatidylethanolamine

FIGURE 3

Schematic summary of the related signalling pathways in the context of exosomes‐mediated autophagy regulation. Exosomes release their cargos into recipient cells that can regulate autophagy. The different effects of exosomes on autophagy regulation and the different signalling pathways affected, primarily due to the different cargos they carry. Exosomal miRNA recognizes its target mRNA, suppresses the translation of target mRNA, and reduces related proteins. The synthesis of mTOR, Beclin‐1, Atgs, and their upstream proteins, are blocked, which in turn affects the process of autophagy

FIGURE 4

Crosstalk between exosome release and the autophagic process. Autophagy can regulate the release of exosomes. As shown in the figure, the amphisomes represent the intersection of exosome biogenesis and the autophagic process. Different autophagic‐related proteins (ATG5, ATG16L1 and LC3B) located on the membrane of MVBs, facilitate exosome biogenesis. Rab7 mediates the transport of MVBS to lysosomes. Rab11 promotes the fusion of MVB and autophagosomes into amphisomes. Rab11, Rab27 and Rab35 are involved in MVBs fusion with the PM to release exosomes. PM, plasma membrane; MVB, multiple vesicle bodies