Lysosomes are membrane-bound organelles for biomolecule degradation and recycling. They also serve as a nutrient sensing and signaling center to maintain cell and tissue homeostasis. Lysosomal properties alter in response to developmental or environmental cues, but these changes are hard to track in vivo. Employing C. elegans as a model system, we have developed assays to examine and quantify lysosome properties in vivo, including lysosome maturation, acidification and cleavage activity. These assays can be used to reveal alterations of lysosomal activity during C. elegans development and in stress conditions.
Cullen PJ, Steinberg F (2018) To degrade or not to degrade: mechanisms and significance of endocytic recycling. Nat Rev Mol Cell Biol 19(11): 679−696
Gan Q, Wang X, Zhang Q, Yin Q, Jian Y, Liu Y, Xuan N, Li J, Zhou J, Liu K, Jing Y, Wang X, Yang C (2019) The amino acid transporter SLC-36.1 cooperates with PtdIns3P 5-kinase to control phagocytic lysosome reformation. J Cell Biol 218(8): 2619−2637
Gonzalez A, Hall MN, Lin SC, Hardie DG (2020) AMPK and TOR: the Yin and Yang of cellular nutrient sensing and growth control. Cell Metab 31(3): 472−492
Hersh BM, Hartwieg E, Horvitz HR (2002) The Caenorhabditis elegans mucolipin-like gene cup-5 is essential for viability and regulates lysosomes in multiple cell types. Proc Natl Acad Sci USA 99(7): 4355−4360
Huizing M, Gahl WA (2020) Inherited disorders of lysosomal membrane transporters. Biochim Biophys Acta Biomembr 1862(12): 183336. https://doi.org/10.1016/j.bbamem.2020.183336
Lawrence RE, Zoncu R (2019) The lysosome as a cellular centre for signalling, metabolism and quality control. Nat Cell Biol 21(2): 133−142
Li Y, Chen B, Zou W, Wang X, Wu Y, Zhao D, Sun Y, Liu Y, Chen L, Miao L, Yang C, Wang X (2016) The lysosomal membrane protein SCAV-3 maintains lysosome integrity and adult longevity. J Cell Biol 215(2): 167−185
Li Y, Tsien RW (2012) pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity. Nat Neurosci 15(7): 1047−1053
Liu B, Du H, Rutkowski R, Gartner A, Wang X (2012) LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino acid homeostasis. Science 337: 351−354
Liu Y, Zou W, Yang P, Wang L, Ma Y, Zhang H, Wang X (2018) Autophagy-dependent ribosomal RNA degradation is essential for maintaining nucleotide homeostasis during C. elegans. Elife 7: e36588. https://doi.org/10.7554/eLife.36588
Miao R, Li M, Zhang Q, Yang C, Wang X (2020) An ECM-to-nucleus signaling pathway activates lysosomes for C. elegans larval development. Dev Cell 52(1): 21−37
Nixon RA (2016) New perspectives on lysosomes in ageing and neurodegenerative disease. Ageing Res Rev 32: 1−1
Parkinson-Lawrence EJ, Shandala T, Prodoehl M, Plew R, Borlace GN, Brooks DA (2010) Lysosomal storage disease: revealing lysosomal function and physiology. Physiology (Bethesda) 25(2): 102−115
Sabatini DD, Adesnik M (2013) Christian de Duve: explorer of the cell who discovered new organelles by using a centrifuge. Proc Natl Acad Sci USA 110(33): 13234−13235
Stoka V, Turk V, Turk B (2016) Lysosomal cathepsins and their regulation in aging and neurodegeneration. Ageing Res Rev 32: 22−37
Sun T, Wang X, Lu Q, Ren H, Zhang H (2011) CUP-5, the C. elegans ortholog of the mammalian lysosomal channel protein MLN1/TRPML1, is required for proteolytic degradation in autolysosomes. Autophagy 7(11): 1308−1315
Sun Y, Li M, Zhao D, Li X, Yang C, Wang X (2020) Lysosome activity is modulated by multiple longevity pathways and is important for lifespan extension in C. elegans. Elife 9: e55745. https://doi.org/10.7554/eLife.55745
Treusch S, Knuth S, Slaugenhaupt SA, Goldin E, Grant BD, Fares H (2004) Caenorhabditis elegans functional orthologue of human protein h-mucolipin-1 is required for lysosome biogenesis. Proc Natl Acad Sci USA 101(13): 4483−4488
Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40OD010440). This work was supported by the National Natural Science Foundation of China (3163001, 91754203), the Ministry of Science and Technology (2016YFA0500203), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19000000) to X. Wang. X. Li is supported by the National Natural Science Foundation of China (31671401).
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.