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In Vivo HIF-Mediated Reductive Carboxylation Is Regulated by Citrate Levels and Sensitizes VHL-Deficient Cells to Glutamine Deprivation
Authors:Paulo A Gameiro  Juanjuan Yang  Ana M Metelo  Rocio Pérez-Carro  Rania Baker  Zongwei Wang  Alexandra Arreola  W Kimryn Rathmell  Aria Olumi  Pilar López-Larrubia  Gregory Stephanopoulos  Othon Iliopoulos
Institution:1. Center for Cancer Research, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA;2. Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA;3. Department of Urology, Massachusetts General Hospital, Boston, MA 02114, USA;4. Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;5. Department of Life Sciences, University of Coimbra, 3004-517 Coimbra, Portugal;6. UNC Lineberger Comprehensive Cancer Center, Departments of Medicine and Genetics, University of North Carolina, Chapel Hill, NC, USA;7. Instituto de Investigaciones Biomédicas “Alberto Sols,” CSIC-UAM, 28029 Madrid, Spain
Abstract:
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  • Highlights? HIF is necessary and sufficient to induce reductive carboxylation in RCC cell lines ? HIF promotes the reductive carboxylation flux by reducing citrate levels ? HIF-expressing tumors display reductive carboxylation in vivo ? HIF renders RCC cells sensitive to glutaminase inhibition in vitro and in vivo
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