Model for NOX2-driven mitochondrial transfer from BMSCs to AML cells. Schematic representing proposed mechanism by which AML cells generates reactive oxygen species (ROS) and creates hypoxic conditions in the bone marrow that are necessary for the mitochondrial transfer from AML cells. NOX2 expressed by AML cells generates high levels of superoxide, which increases the oxidative stress in the BMSCs and stimulates the formation of TNTs from the membrane of AML cells to the BMSCs. The increased oxidative state in the BMSC triggers the mitochondrial transfer from BMSCs to AML cells, which will in turn increase mitochondria respiration and adenosine triphosphate (ATP) generations in the AML cells. Cytochalasin (inhibitor of actin polymerization) and diphenyleneiodonium (DPI, an inhibitor of NOX2) block mitochondrial transfer. Hydrogen peroxide (H₂O₂) and the chemotherapy agent daunorubicin increase mitochondrial transfer. Professional illustration by Patrick Lane, ScEYEnce Studios.