Figure 1.

Redox and metabolic status of HSC versus LSC and chemoresistant cells. HSC are characterized by low metabolic activity and ROS levels. The low ATP levels they need come from glycolysis as they have immature mitochondria which suffer mitophagy. Low NOX levels and mitochondrial metabolism could explain the low ROS levels of HSC, which do not require high antioxidant systems to keep them under control. However, LSC actively obtain energy mainly by glycolysis (thick arrow) but also from TCA and FAO (thin arrows). This active metabolism provokes the production of ROS that are quenched by overexpressed antioxidant systems. On the right side of the figure, chemoresistant cells also produce ATP by glycolysis although they show mature and fused mitochondria which render high OXPHOS, being fed by hyperactivated TCA and FAO. Augmented OXPHOS and NOX result in high ROS levels which cannot be extinguished despite high antioxidant systems. ETC, electron transport chain; FAO, fatty acid oxidation; HSC, hematopoietic stem cells; LSC, leukemic stem cells; NOX, NADPH oxidase; OXPHOS, oxidative phosphorylation; TCA, tricarboxylic acid.