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. 2021 May 5;220(6):e202102001. doi: 10.1083/jcb.202102001

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© 2021 Yang and Wang

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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Figure 4. — Role of lysosome biogenesis and function in development and aging. (A) The correlation between lysosomes and the different states of NSCs or HSCs. qNSCs and qHSCs have larger and more abundant lysosomes with lower degradation activity (indicated in pink). qNSCs exhibit an age-dependent decrease in lysosome levels (indicated in blue). (B) The correlation between lysosomes and the asymmetric division and differentiation of HSCs. Lysosomes are asymmetrically distributed to daughter cells, and the daughter cells with low levels of lysosomes are metabolically active and induced to differentiate. (C) STA-2– and ELT-3–dependent lysosome biogenesis in ECM remodeling during C. elegans molt. During molt, the cuticle-epidermis attachments are damaged and detected by STA-2. STA-2 translocates to the nucleus and functions together with ELT-3 to activate the expression of lysosomal V-ATPase genes. This accelerates lysosome maturation at molt and facilitates the ECM remodeling required for larval development. (D) The correlation between lysosome biogenesis and lifespan in C. elegans. In aging C. elegans, lysosomes show reduced vesicular morphology; increased tubular morphology; increased mean and total volume; and decreased acidity, motility, and degradation activity. In long-lived mutants from three different longevity pathways, lysosomal gene expression is up-regulated, which requires DAF-16/FOXO and SKN-1/NRF2. Lysosome morphology and activity are well maintained during aging.