Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular - PubMed (original) (raw)

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Lysosomal Exocytosis, Exosome Release and Secretory Autophagy: The Autophagic- and Endo-Lysosomal Systems Go Extracellular

Sandra Buratta et al. Int J Mol Sci. 2020.

Abstract

Beyond the consolidated role in degrading and recycling cellular waste, the autophagic- and endo-lysosomal systems play a crucial role in extracellular release pathways. Lysosomal exocytosis is a process leading to the secretion of lysosomal content upon lysosome fusion with plasma membrane and is an important mechanism of cellular clearance, necessary to maintain cell fitness. Exosomes are a class of extracellular vesicles originating from the inward budding of the membrane of late endosomes, which may not fuse with lysosomes but be released extracellularly upon exocytosis. In addition to garbage disposal tools, they are now considered a cell-to-cell communication mechanism. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in unconventional protein secretion and autophagy-dependent secretion, which are fundamental mechanisms for toxic protein disposal, immune signalling and pathogen surveillance. These cellular processes underline the crosstalk between the autophagic and the endosomal system and indicate an intersection between degradative and secretory functions. Further, they suggest that the molecular mechanisms underlying fusion, either with lysosomes or plasma membrane, are key determinants to maintain cell homeostasis upon stressing stimuli. When they fail, the accumulation of undigested substrates leads to pathological consequences, as indicated by the involvement of autophagic and lysosomal alteration in human diseases, namely lysosomal storage disorders, age-related neurodegenerative diseases and cancer. In this paper, we reviewed the current knowledge on the functional role of extracellular release pathways involving lysosomes and the autophagic- and endo-lysosomal systems, evaluating their implication in health and disease.

Keywords: amphisomes; autophagosomes; exosomes; extracellular vesicles; lysosomal exocytosis; secretory autophagy; unconventional protein secretion.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Overview of lysosomal exocytosis, exosome release and autophagy-dependent secretory pathways. Lysosomal exocytosis leads to the secretion of lysosomal content upon lysosome fusion with plasma membrane. Exosomes originate from the inward budding of late endosome membrane, which originates MVBs. They are either released extracellularly upon exocytosis or degraded into lysosomes. Autophagy is a cellular process leading to sequestration of cytosolic cargoes for their degradation within lysosomes. However, the autophagic machinery is also involved in autophagy-dependent secretion of autophagosomes. In addition to merging with lysosomes or plasma membrane, autophagosomes can also fuse with late endosomes/MVBs to produce amphisomes. In turn, amphisomes can either fuse with lysosomes to degrade their content or with plasma membrane. The red arrows indicate fusion with plasma membrane, the green arrows, fusion with lysosome, and the black arrows, pathways leading to organelle maturation and to the intersection between autophagic and endocytic pathway.

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