Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations.

@article{Chen2018RewiringOG,
  title={Rewiring of Glutamine Metabolism Is a Bioenergetic Adaptation of Human Cells with Mitochondrial DNA Mutations.},
  author={Qiuying Chen and Kathryne Kirk and Yevgeniya I. Shurubor and Dazhi Zhao and Andrea J. Arreguin and Ifrah Shahi and Federica Valsecchi and Guido Primiano and Elizabeth L Calder and V Carelli and Travis T Denton and Myron Flint Beal and Steven S. Gross and Giovanni Manfredi and Marilena D'Aurelio},
  journal={Cell metabolism},
  year={2018},
  volume={27 5},
  pages={1007-1025.e5}
}
Using molecular, biochemical, and untargeted stable isotope tracing approaches, we identify a previously unappreciated glutamine-derived α-ketoglutarate (αKG) energy-generating anaplerotic flux to be critical in mitochondrial DNA (mtDNA) mutant cells that harbor human disease-associated oxidative phosphorylation defects. Stimulating this flux with αKG supplementation enables the survival of diverse mtDNA mutant cells under otherwise lethal obligatory oxidative conditions. Strikingly, we… CONTINUE READING
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