Reversal of mitochondrial malate dehydrogenase 2 enables anaplerosis via redox rescue in respiration-deficient cells
Patricia Altea‐Manzano, Anke Vandekeere, Joy Edwards-Hicks, Mar Roldán, Emily Abraham, Xhordi Lleshi, Ania Naila Guerrieri, Domenica Berardi, Jimi Wills, Jair Marques, Asimina Pantazi, Juan Carlos Acosta, Rosario M. Sánchez‐Martín, Sarah‐Maria Fendt, Miguel Martı́n, Andrew J. Finch
Abstract
-dependent activity of the mitochondrial glutamate dehydrogenase (GDH) and thereby enables anaplerosis-the entry of glutamine-derived carbon into the TCA cycle and connected biosynthetic pathways. Thus, under impaired ETC function, the cytosolic redox state is communicated into the mitochondrion and acts as a rheostat to support GDH activity and cell viability.
Topics & Concepts
BiologyMalate dehydrogenaseMitochondrionRedoxRespirationDehydrogenaseCell biologyBiochemistryCellular respirationMolecular biologyEnzymeBotanyMaterials scienceMetallurgyCancer, Hypoxia, and MetabolismMetabolism and Genetic DisordersPancreatic function and diabetes