Kynurenine importation by SLC7A11 propagates anti-ferroptotic signaling.

ABSTRACT: IDO1 oxidizes tryptophan (TRP) to generate kynurenine (KYN), the substrate for 1-carbon and NAD metabolism, and is implicated in pro-cancer pathophysiology and infection biology. However, the mechanistic relationships between IDO1 in amino acid depletion versus product generation have remained a longstanding mystery. We found an unrecognized link between IDO1 and cell survival mediated by KYN that serves as the source for molecules that inhibit ferroptotic cell death. We show that this effect requires KYN export from IDO1-expressing cells, which is then available for non-IDO1-expressing cells via SLC7A11, the central transporter involved in ferroptosis suppression. Whether inside the "producer" IDO1⁺ cell or the "receiver" cell, KYN is converted into downstream metabolites, supp

SUBMITTER: Fiore A 

PROVIDER: S-EPMC7617904 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature