PT - JOURNAL ARTICLE AU - Adelita D. Mendoza AU - Nicholas Dietrich AU - Chieh-Hsiang Tan AU - Daniel Herrera AU - Jennysue Kasiah AU - Zachary Payne AU - Daniel L. Schneider AU - Kerry Kornfeld TI - Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis AID - 10.1101/2021.09.18.460850 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.09.18.460850 4099 - http://biorxiv.org/content/early/2021/09/19/2021.09.18.460850.short 4100 - http://biorxiv.org/content/early/2021/09/19/2021.09.18.460850.full AB - Lysosome-related organelles play evolutionarily conserved roles in zinc storage, but mechanisms that control zinc flow in and out are not well understood. In C. elegans intestinal cells, the CDF-2 transporter stores zinc in these organelles during excess. Here we identify ZIPT-2.3 as the transporter that releases zinc during deficiency. The expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated in zinc excess and deficiency, establishing a fundamental mechanism of homeostasis. Super-resolution microscopy demonstrated these organelles are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment inflates during zinc excess and deficiency by vesicle fusion delivering zinc transporters. These results identify an unexpected structural feature of lysosome-related organelles that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis.Competing Interest StatementThe authors have declared no competing interest.