PLoS Genetics · Published 2026-06-22 · DOI 10.1371/journal.pgen.1012199
Chaoyi Xie, Yi Luo, Yawen Zheng, Bowen Liu, Shibo Song, Jie Wei, Anbing Shi, Yanling Yan
Elevated environmental zinc levels pose significant toxicity to biological systems, necessitating adaptive responses to mitigate excessive zinc exposure. In C. elegans, a specific lysosome-related organelle, the gut granule, may increase in number and volume with high dietary zinc, thereby lowering cytosolic zinc concentration, though the mechanisms remain unclear. Our results suggest that GLO-1 predominantly controls granule biogenesis, whereas zinc-induced granule expansion involves distinct mechanisms. Further study revealed that high zinc upregulated GLO-1 activity through its GEF complex GLO-3-CCZ-1, by enhancing transcription of GLO-3 and post-translational modification of CCZ-1. Zinc transporter CDF-2 has been identified to mediate zinc influx into gut granules. In this study, analysis of 14 C. elegans CDFs reveals that ZK185.5 (CDF-3) and F19C6.5 (CDF-4) also localize in gut granules. Functional studies suggest that CDF-3, not CDF-4, complements CDF-2 in facilitating zinc influx into gut granules. Unlike CDF-2, the expression of CDF-3 is downregulated in a high zinc diet. These results suggest a modulation in the composition of CDFs within gut granules in response to environmental zinc. Together, our study reveals a sophisticated zinc detoxification mechanism of C. elegans gut granule to uphold cytosolic zinc homeostasis amidst fluctuating environments.
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Xie, C., Luo, Y., Zheng, Y., et al. (2026). Lysosome-related organelles employ divergent mechanisms to modulate cytosolic zinc homeostasis. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1012199