cells Review Energy Metabolism in IDH1 Wild-Type and IDH1-Mutated Glioblastoma Stem Cells: A Novel Target for Therapy? Cornelis J.F. van Noorden 1,2,*, Vashendriya V.V. Hira 1, Amber J. van Dijck 2 , Metka Novak 1, Barbara Breznik 1 and Remco J. Molenaar 1,3 1 Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, VeˇcnaPot 111, 1000 Ljubljana, Slovenia;
[email protected] (V.V.V.H.);
[email protected] (M.N.);
[email protected] (B.B.);
[email protected] (R.J.M.) 2 Department of Medical Biology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands;
[email protected] 3 Department of Medical Oncology, Amsterdam UMC Location Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands * Correspondence:
[email protected]; Tel.: +31-638-639-561 Abstract: Cancer is a redox disease. Low levels of reactive oxygen species (ROS) are beneficial for cells and have anti-cancer effects. ROS are produced in the mitochondria during ATP production by oxidative phosphorylation (OXPHOS). In the present review, we describe ATP production in primary brain tumors, glioblastoma, in relation to ROS production. Differentiated glioblastoma cells mainly use glycolysis for ATP production (aerobic glycolysis) without ROS production, whereas glioblastoma stem cells (GSCs) in hypoxic periarteriolar niches use OXPHOS for ATP and ROS production, which is modest because of the hypoxia and quiescence of GSCs. In a significant proportion of glioblastoma, Citation: van Noorden, C.J.F.; Hira, isocitrate dehydrogenase 1 (IDH1) is mutated, causing metabolic rewiring, and all cancer cells use V.V.V.; van Dijck, A.J.; Novak, M.; OXPHOS for ATP and ROS production.