Lysosomal iron recycling in mouse macrophages is dependent upon both LcytB and Steap3 reductases.

ABSTRACT: Iron that is stored in macrophages as ferritin can be made bioavailable by degrading ferritin in the lysosome and releasing iron back into the cytosol. Iron stored in ferritin is found as Fe3+ and must be reduced to Fe2+ before it can be exported from the lysosome. Here we report that the lysosomal reductase Cyb561a3 (LcytB) and the endosomal reductase six-transmembrane epithelial antigen of prostate 3 (Steap3) act as lysosomal ferrireductases in the mouse macrophage cell line RAW264.7 converting Fe3+ to Fe2+ for iron recycling. We determined that when lysosomes were loaded with horse cationic ferritin, reductions or loss of LcytB or Steap3 using CRISPR/Cas9-mediated knockout technology resulted in decreased lysosomal iron export. Loss of both reductases was additive in decreasing lysosoma

SUBMITTER: Meng F 

PROVIDER: S-EPMC8941456 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature