An autoamplification loop links mitochondrial dynamics and ROS production to onset of thrombopoiesis. Onset of thrombopoiesis from mature round MKs occurs when a positive oxygen gradient is present between the extravascular edge of the sinusoids, where the MKs are located, and the blood flow. It is characterized by cell deformation (loss of MK roundness) and cytoskeletal reorganization (loss of MLC phosphorylation) of intermediate MKs, followed by the formation of extended cell protrusions resulting in terminal proplatelet-forming MKs. This loss of roundness is preceded by a strong recruitment of active pDrp1 to mitochondria that triggers fission within nondeformed, round MKs. Mitochondrial fission and ROS production are triggered by the positive oxygen gradient, which favors additional mitochondrial pDrp1 recruitment, additional fission, and ROS production in an autoamplifying loop that is necessary for thrombopoiesis to proceed, allowing for the formation of long intravascular proplatelet extensions filled with small, well-delineated mitochondria in terminal MKs.