Figure 1. Mitochondria and metabolism in hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). HSCs reside in a hypoxic niche with low amounts of growth factors. This environment fosters the activation of transcription factors such as HIF1A, FOXO, and PPARD and the inhibition of AKT kinase. This paradigm facilitates fatty acid oxidation, reduced mitochondrial content (via de-repressing TSC, which inhibits MTOR-mediated mitochondrial biogenesis and FOXO-mediated inhibition of nuclear-encoded mitochondrial biogenesis), lower amounts of ROS, and increased anaerobic glycolysis. Autophagy has been implicated in HSC maintenance, but it is unclear which function of autophagy is critical—clearance of damaged mitochondria or recycling of metabolites. A metabolic shift occurs with commitment of HSCs to differentiate, leading to suppression of fatty acid oxidation and anaerobic glycolysis, increases in mitochondrial content and oxidative phosphorylation, and higher levels of ROS, which are at least partially mediated through AKT and MTOR. The role of autophagy in committed hematopoietic progenitor cells remains unclear. FA, fatty acids; AA, amino acids; TCA, tricarboxylic acid cycle.