Yin/yang bidirectional exchange of mitochondria between MSC and HSC/LSC during chemotherapy and hematopoietic recovery following TBI. (A) Chemotherapy causes excessive mitochondrial-derived ROS levels in leukemic stem cells (LSC) and triggers mitochondrial donation from MSCs favoring LSC chemoresistance and relapse. (B) TBI reduces mitochondrial function and ROS levels in BM-MSC, but high ATP levels and low AMPK activity in transplanted HSCs promote Cx43- and cell-contact-dependent mitochondrial transfer from HSCs/progenitors to MSCs, favoring both stromal and hematopoietic regeneration.