![]() We found that induction of reductive carboxylation commonly requires enhanced tyrosine phosphorylation and activation of IDH1, which, surprisingly, is achieved by attenuation of a cytosolic protein tyrosine phosphatase, Src homology region 2 domain-containing phosphatase-2 (SHP-2). However, whether diverse cellular signals induce reductive carboxylation differentially or through a common signaling converging node remains unclear. Reductive carboxylation is often dependent on cytosolic isocitrate dehydrogenase 1 (IDH1). This metabolic process contributes to redox homeostasis and sustains biosynthesis of lipids. Electronic address: onĮnvironmental 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. Electronic address: 8 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. Electronic address: 7 UT Southwestern Medical Center, Dallas, TX 75390, USA. ![]() 6 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.5 The Ben May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.4 Department of Pediatrics and Aflac Cancer and Blood Disorder Center, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.3 Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.2 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.1 Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
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