Article
Fumarate induces redox-dependent senescence by modifying glutathione metabolism.
Nature communications - 23 Jan 2015
Zheng Liang, Cardaci Simone, Jerby Livnat, MacKenzie Elaine D, Sciacovelli Marco, Johnson T Isaac, Gaude Edoardo, King Ayala, Leach Joshua D G, Edrada-Ebel RuAngelie, Hedley Ann, Morrice Nicholas A, Kalna Gabriela, Blyth Karen, Ruppin Eytan, Frezza Christian, Gottlieb Eyal
Abstract excerpt
Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) are associated with a highly malignant form of renal cancer. We combined analytical chemistry and metabolic computational modelling to investigate the metabolic implications of FH loss in immortalized and primary mouse kidney cells. Here, we show that the accumulation of fumarate caused by the inactivation of FH leads to oxidative...
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