Connecting Mitochondria, Metabolism, and Stem Cell Fate - PubMed (original) (raw)

Pathways involved in the interplay between pluripotency, mitochondrial biogenesis, and metabolism. On the one hand, energy-, nutrient-, and environment-sensing pathways regulate both pluripotency and metabolism through their effects on glycolysis and mitochondrial biogenesis and activity. On the other hand, mitochondrial activity regulates stemness and differentiation through various mechanisms. These involve, for example, the production of ROS, which can induce or prevent the commitment to specific differentiation lineages; the production of intermediates or cofactors influencing epigenetic marks, protein activity, and stability; and the modification of the redox or energy status of the cells, thus altering nutrient- and energy-sensing pathways. AMPK, AMP-activated protein kinase; IF1, inhibitory factor I; LKB1, liver kinase B1; HIF-1α, hypoxia-inducible factor1α; mTORC1, mammalian target of rapamycin complex I; PDH, pyruvate dehydrogenase; PDK, pyruvate dehydrogenase kinase; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator 1α; PHD, prolyl hydroxylase domain-containing protein; PKCλ/ι, protein kinase C isoform lambda/iota; TCA, tricarboxilic acid; TSC2, tuberous sclerosis complex 2; α-KG, α-ketoglutarate. Color images available online at