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

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.

SUBMITTER: Buratta S

PROVIDER: S-EPMC7178086 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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

Buratta Sandra S Tancini Brunella B Sagini Krizia K Delo Federica F Chiaradia Elisabetta E Urbanelli Lorena L Emiliani Carla C

International journal of molecular sciences 20200408 7

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, w ...[more]

PMID: 32276321

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Project description:The autophagic degradation of lipid droplets (LDs), termed lipophagy, is a major mechanism that contributes to lipid turnover in numerous cell types. While numerous factors, including nutrient deprivation or overexpression of PNPLA2/ATGL (patatin-like phospholipase domain containing 2) drive lipophagy, the trafficking of fatty acids (FAs) produced from this pathway is largely unknown. Herein, we show that PNPLA2 and nutrient deprivation promoted the extracellular efflux of FAs. Inhibition of autophagy or lysosomal lipid degradation attenuated FA efflux highlighting a critical role for lipophagy in this process. Rather than direct transport of FAs across the lysosomal membrane, lipophagy-derived FA efflux requires lysosomal fusion to the plasma membrane. The lysosomal Ca2+ channel protein MCOLN1/TRPML1 (mucolipin 1) regulates lysosomal-plasma membrane fusion and its overexpression increased, while inhibition blocked FA efflux. In addition, inhibition of autophagy/lipophagy or MCOLN1, or sequestration of extracellular FAs with BSA attenuated the oxidation and re-esterification of lipophagy-derived FAs. Overall, these studies show that the well-established pathway of lysosomal fusion to the plasma membrane is the primary route for the disposal of FAs derived from lipophagy. Moreover, the efflux of FAs and their reuptake or subsequent extracellular trafficking to adjacent cells may play an important role in cell-to-cell lipid exchange and signaling.Abbreviations: ACTB: beta actin; ADRA1A: adrenergic receptor alpha, 1a; ALB: albumin; ATG5: autophagy related 5; ATG7: autophagy related 7; BafA1: bafilomycin A1; BECN1: beclin 1; BHBA: beta-hydroxybutyrate; BSA: bovine serum albumin; CDH1: e-cadherin; CQ: chloroquine; CTSB: cathepsin B; DGAT: diacylglycerol O-acyltransferase; FA: fatty acid; HFD: high-fat diet; LAMP1: lysosomal-associated membrane protein 1; LD: lipid droplet; LIPA/LAL: lysosomal acid lipase A; LLME: Leu-Leu methyl ester hydrobromide; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; MCOLN1/TRPML1: mucolipin 1; MEF: mouse embryo fibroblast; PBS: phosphate-buffered saline; PIK3C3/VPS34: phosphatidylinositol 3-kinase catalytic subunit type 3; PLIN: perilipin; PNPLA2/ATGL patatin-like phospholipase domain containing 2; RUBCN (rubicon autophagy regulator); SM: sphingomyelin; TAG: triacylglycerol; TMEM192: transmembrane protein 192; VLDL: very low density lipoprotein.

Dataset Information

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

Publications

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

Similar Datasets

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