Empowering self-renewal and differentiation: the role of mitochondria in stem cells

Stem cells are characterized by their multi-lineage differentiation potential (pluripotency) and their ability for self-renewal, which permits them to proliferate while avoiding lineage commitment and senescence. Recent studies demonstrate that undifferentiated, pluripotent stem cells display lower levels of mitochondrial mass and oxidative phosphorylation, and instead preferentially use non-oxidative glycolysis as a major source of energy. Hypoxia is a potent suppressor of mitochondrial oxidation and appears to promote “stemness” in adult and embryonic stem cells. This has lead to an emerging paradigm, that mitochondrial oxidative metabolism is not just an indicator of the undifferentiated state of stem cells, but may also regulate the pluripotency and self-renewal of stem cells. The identification of specific mitochondrial pathways that regulate stem cell fate may therefore enable metabolic programming and reprogramming of stem cells.