Abstract
Lysosomes are acidic cell compartments containing a large set of hydrolytic enzymes. These lysosomal hydrolases degrade proteins, lipids, polysaccharides, and nucleic acids into their constituents. Materials to be degraded can reach lysosomes either from inside the cell, by autophagy, or from outside the cell, by different forms of endocytosis. In addition to their degradative functions, lysosomes are also able to extracellularly release their contents by lysosomal exocytosis. These organelles move from the perinuclear region along microtubules towards the proximity of the plasma membrane, then the lysosomal and plasma membrane fuse together via a Ca2+-dependent process. The fusion of the lysosomal membrane with plasma membrane plays an important role in plasma membrane repair, while the secretion of lysosomal content is relevant for the remodelling of extracellular matrix and release of functional substrates. Lysosomal storage disorders (LSDs) and age-related neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases, share as a pathological feature the accumulation of undigested material within organelles of the endolysosomal system. Recent studies suggest that lysosomal exocytosis stimulation may have beneficial effects on the accumulation of these unprocessed aggregates, leading to their extracellular elimination. However, many details of the molecular machinery required for lysosomal exocytosis are only beginning to be unravelled. Here, we are going to review the current literature on molecular mechanisms and biological functions underlying lysosomal exocytosis, to shed light on the potential of lysosomal exocytosis stimulation as a therapeutic approach.
Highlights
Lysosomes are intracellular organelles surrounded by a single membrane and displaying a round morphology, first discovered by C
Most lysosomes are localized around the nucleus and the microtubule-organizing centre (MTOC) [11], but a pre-requisite for lysosomal exocytosis is their transport in the proximity of the plasma membrane [60]
Ca2+ release is regulated via transcription factor EB (TFEB), which increases the transcriptional activation of the lysosomal Ca2+ channel TRPML1, inducing the fusion of lysosomes with the plasma membrane [55]
Summary
Lysosomes are intracellular organelles surrounded by a single membrane and displaying a round morphology, first discovered by C. Regulation of this movement by interaction withlong the cytoskeleton plays fundamental rolebags”, in lysosomal exocytosis In this regarded manuscript, we are going to been considered justa “waste disposal are more correctly as metabolic hubs, review the current knowledge on lysosomal exocytosis, describe the underlying molecular whose degradative function is regulated by specific nutrient sensing mechanisms, according to mechanisms, and focuslysosomes our attention on the recent findings concerning thethe role lysosomal cell needs [5]. To carry out these tasks, lysosomes move close to the plasma membrane and fuse with it in response to specific stimuli The regulation of this movement by interaction with the cytoskeleton plays a fundamental role in lysosomal exocytosis. The pathological implication of lysosomal exocytosis and the targeting of this process for therapeutic purpose will be discussed
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