Top: Xanthine stone in the posterior intestine of xdh-1; sulp-4 mutant C. elegans. Bottom: Schematic showing that in wild-type (left) C. elegans, sulfur amino acid catabolism gives rise to sulfate which is maintained at homeostatic levels by SULP-4-mediated exchange with the environment via the excretory cell. During sulp-4 loss of function (right), CTH-2/CDO-1-derived sulfates accumulate causing osmotic imbalance. This osmotic imbalance promotes a maladaptive positive feedback loop promoting additional cdo-1 mRNA accumulation. This cascade culminates in embryonic lethality, altered larval development, and a propensity to form xanthine stones when XDH-1 activity is compromised.
Xanthine dehydrogenase mutations can cause #xanthinuria in humans. This study in #Celegans provides new insights into the mechanisms of #xanthine #KidneyStone accumulation, implicating sulfate imbalance & osmotic stress in disease progression @plosbiology.org 🧪 plos.io/4pXOCFh
