Hematopoietic stem cell-derived conditioned media (HSC-CM) compromises the mitochondrial dynamics by inducing excessive mitochondrial fission in colorectal cancer (CRC) cells. This occurs via upregulation of DRP-1 and it’s complex protein. The excessive fission leads to severe mitochondrial dysfunction, characterized by a loss of mitochondrial membrane potential (MMP) and impaired bioenergetics, including decreased ATP production and disrupted electron transport chain (ETC) complexes. This energy crisis and overproduction of reactive oxygen species (ROS) ultimately trigger intrinsic apoptosis and mitophagy, leading to the clearance of CRC cells.