Mitophagy: a key regulator of hematopoietic stem cell fate

Hematopoietic stem cells (HSCs) continuously regenerate all blood and immune cell types throughout life and are also capable of self-renewal. Adult HSCs reside in bone marrow niches with almost no blood perfusion. Such highly hypoxic environment brings HSCs towards a preferentially anaerobic glycolysis based metabolism rather than a mitochondrial oxidative phosphorylative one. However, new studies show that this metabolic state is not just a mere adaptation to stem cell niche extreme microenvironment but correlate with HSCs ability to maintain stemness and differentiation potential through regulation of mitochondrial activity. Mitophagy, by maintaining a low metabolic state, plays an essential role in preserving HSC regeneration potential and in regulating self-renewal. Interestingly, the activation of specific metabolic pathways, by regulating autophagy, can also impact on HSC stemness potential.