Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells.

ABSTRACT: Environmental stresses, including hypoxia or detachment for anchorage independence, or attenuation of mitochondrial respiration through inhibition of electron transport chain induce reductive carboxylation in cells with an enhanced fraction of citrate arising through reductive metabolism of glutamine. This metabolic process contributes to redox homeostasis and sustains biosynthesis of lipids. Reductive carboxylation is often dependent on cytosolic isocitrate dehydrogenase 1 (IDH1). However, whether diverse cellular signals induce reductive carboxylation differentially or through a common signaling converging node remains unclear. We found that induction of reductive carboxylation commonly requires enhanced tyrosine phosphorylation and activation of IDH1, which, surprisingly, is achieved by

SUBMITTER: Zhang R 

PROVIDER: S-EPMC9308720 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature