Hematopoietic stem cell (HSC) divisional memory: The journey of mitochondrial metabolism through HSC division

•HSC functions are inversely correlated with their divisional history.•Mitochondria remodeling occurs in HSCs throughout the cell cycle.•Mitochondria-driven metabolic adaptation drives HSC functional decline.•Mitochondria-driven metabolic adaptation may keep HSC divisional memory. Hematopoietic stem cells (HSCs) are characterized by their ability to produce all cells of the blood and immune system and have been used for transplantation for decades. Although the regenerative potential of HSCs is high, their self-renewal potential is limited. HSC functions are inversely correlated with their divisional history. Recent advances in our understanding of the regulation of HSCs through cell division suggest that HSCs may never replicate into identical self, but rather replicate into progeny that gradually lose functionality at each round of division. HSC division is accompanied by major transcriptional and metabolic changes. In this perspective, the possibility that mitochondrial metabolism confers HSC division memory and programs HSCs for extinction is discussed.