The multifaceted role of mitochondria in HSC fate decisions: energy and beyond

•Mitochondria are critical regulators of hematopoietic stem cell (HSC) functions •Mitochondria control HSC cell cycle entry •Mitochondrial metabolism controls asymmetric HSC fate decisions •Mitochondria become defective with age and replicative stress •Mitochondria can be targeted to improve HSC functions Hematopoietic stem cells (HSCs) have the properties to self-renew and/or differentiate into all-mature blood cell lineages. The fate decisions to generate progeny that retain stemness properties or that commit to differentiation is a fundamental process to maintain tissue homeostasis and must be tightly regulated to prevent HSC overgrowth or exhaustion. HSC fate decisions are inherently coupled to cell division. The transition from quiescence to activation is accompanied by major metabolic and mitochondrial changes that are important for cell cycle entry and for balanced decisions between self-renewal and differentiation. In this review, we discuss the current understanding of the role of mitochondrial metabolism in HSC transition from quiescence to activation and fate decisions. Hematopoietic stem cells (HSCs) have the properties to self-renew and/or differentiate into all-mature blood cell lineages. The fate decisions to generate progeny that retain stemness properties or that commit to differentiation is a fundamental process to maintain tissue homeostasis and must be tightly regulated to prevent HSC overgrowth or exhaustion. HSC fate decisions are inherently coupled to cell division. The transition from quiescence to activation is accompanied by major metabolic and mitochondrial changes that are important for cell cycle entry and for balanced decisions between self-renewal and differentiation. In this review, we discuss the current understanding of the role of mitochondrial metabolism in HSC transition from quiescence to activation and fate decisions.