The immunometabolite itaconate inhibits heme synthesis and remodels cellular metabolism in erythroid precursors.

ABSTRACT: As part of the inflammatory response by macrophages, Irg1 is induced, resulting in millimolar quantities of itaconate being produced. This immunometabolite remodels the macrophage metabolome and acts as an antimicrobial agent when excreted. Itaconate is not synthesized within the erythron but instead may be acquired from central macrophages within the erythroid island. Previously, we reported that itaconate inhibits hemoglobinization of developing erythroid cells. Herein we show that this action is accomplished by inhibition of tetrapyrrole synthesis. In differentiating erythroid precursors, cellular heme and protoporphyrin IX synthesis are reduced by itaconate at an early step in the pathway. In addition, itaconate causes global alterations in cellular metabolite pools, resulting in eleva

SUBMITTER: Marcero JR 

PROVIDER: S-EPMC9153040 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature