With additional membrane and content sorting, lysosomes are reformed or regenerated ( Saffi and Botelho, 2019 Yang and Wang, 2021). Upon completion of degradation, autolysosomes and endolysosome hybrids undergo membrane remodeling and fission: budding, vesiculation, tubulation, and scission ( Luzio et al., 2007b Saffi and Botelho, 2019). Because the total volume is increased after membrane fusion due to a change in the surface-area-to-volume ratio, solute/water flux is involved in keeping the secondary lysosomes isotonic ( Li et al., 2020). Hydrolase-mediated degradation then takes place in the resulting secondary lysosomes, such as autolysosomes, phagolysosomes, and endolysosomes ( Ballabio and Bonifacino, 2020 Huotari and Helenius, 2011). Primary lysosomes receive cargo through membrane fusion with autophagosomes and late endosomes ( Huotari and Helenius, 2011 Luzio et al., 2007b). Similar membrane addition/retrieval and solute/water flux mechanisms operate in intracellular membranous compartments, such as macropinosomes, phagosomes, autophagosomes, endosomes, and lysosomes ( Freeman et al., 2020 Li et al., 2020). Hence, the plasma membrane possesses a variety of mechanisms that regulate endocytosis and exocytosis, membrane stretching and relaxation, as well as solute and water flux. Additionally, endocytosis of the extracellular fluid may also be involved in this response ( Wang et al., 2011). Conversely, when cells are under hypertonic conditions or apoptotic cell death, a regulatory volume increase (RVI) response (see text box) is adaptively triggered, in which solute and water influx are involved ( Hoffmann et al., 2009 Jentsch, 2016). In addition, exocytosis of intracellular vesicles may also help relieve plasma membrane tension ( Okada et al., 1992 Truschel et al., 2002). The RVD is believed to be mediated by plasma membrane Cl −/K + efflux and subsequently passive extrusion of osmotically obligated H 2O from the cytosol ( Lang et al., 1998). To protect cells from necrotic cell death, a regulatory volume decrease (RVD) response (see text box) must be triggered ( Hoffmann et al., 2009). Upon net water influx under hypotonic conditions, cells become swollen while the plasma membrane is stretched if the membrane tension is not relieved, cells may undergo necrosis or burst ( Ritter et al., 2021 Shubin et al., 2016). We also provide perspectives on how lysosomes may adjust the volume of themselves, the cytosol, and the cytoplasm through the control of lysosomal solute and water transport.Ĭells must maintain the volume constancy of the cytosol and cytoplasm (see text box) during osmotic water shifts, cell proliferation and death, and metabolically produced content changes ( Hoffmann et al., 2009 Jentsch, 2016 Lang et al., 1998). Lysosomal H +, Na +, K +, Ca 2+, and Cl − channels and transporters sense trafficking and osmotic cues to regulate both solute flux and membrane trafficking. In this review, we discussed the mechanisms that regulate lysosomal fusion and fission as well as swelling and condensation, with a focus on solute and water transport mechanisms across lysosomal membranes. As a membranous organelle filled with cargo macromolecules, catabolites, ions, and hydrolases, the lysosome must have mechanisms that regulate its shape and size while coordinating content exchange. During hypoosmotic stress or when undigested materials accumulate, lysosomes become swollen and hypo-functional. Lysosome function requires an osmo-sensing machinery that regulates osmolytes (ions and organic solutes) and water flux. Lysosomes mediate hydrolase-catalyzed macromolecule degradation to produce building block catabolites for reuse.
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