Facilitative lysosomal transport of bile acids alleviates ER stress in mouse hematopoietic precursors.

ABSTRACT: Mutations in human equilibrative nucleoside transporter 3 (ENT3) encoded by SLC29A3 results in anemia and erythroid hypoplasia, suggesting that ENT3 may regulate erythropoiesis. Here, we demonstrate that lysosomal ENT3 transport of taurine-conjugated bile acids (TBA) facilitates TBA chemical chaperone function and alleviates endoplasmic reticulum (ER) stress in expanding mouse hematopoietic stem and progenitor cells (HSPCs). Slc29a3^-/- HSPCs accumulate less TBA despite elevated levels of TBA in Slc29a3^-/- mouse plasma and have elevated basal ER stress, reactive oxygen species (ROS), and radiation-induced apoptosis. Reintroduction of ENT3 allows for increased accumulation of TBA into HSPCs, which results in TBA-mediated alleviation of ER stress and erythroid apoptosis.

SUBMITTER: Persaud AK 

PROVIDER: S-EPMC7902824 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature