HSC are highly heterogeneous in their mitochondrial metabolism, and the quiescence and potency of HSC depend on the status of mitochondrial dynamics and the clearance of damaged mitochondria. Recent evidence has shown that in stress response, BM stromal cells transfer healthy mitochondria to HSC, facilitate HSC bioenergetics shift towards oxidative phosphorylation, and subsequently stimulate leukocyte expansion. Furthermore, metabolic rewiring following mitochondria transfer from HSPC to BM stromal cells likely to repair the damaged BM niche and accelerate limiting HSC transplantation post myeloablative conditioning.