Mitochondrial fusion-fission dynamics and its involvement in colorectal cancer

The incidence and mortality rates of colorectal cancer have elevated its status as a significant public health concern. Recent research has elucidated the crucial role of mitochondrial fusion-fission dynamics in the initiation and progression of colorectal cancer. Elevated mitochondrial fission or fusion activity can contribute to the metabolic reprogramming of tumor cells, thereby activating oncogenic pathways that drive cell proliferation, invasion, migration, and drug resistance. Nevertheless, excessive mitochondrial fission can induce apoptosis, whereas moderate mitochondrial fusion can protect cells from oxidative stress. This imbalance in mitochondrial dynamics can exert dual roles as both promoters and inhibitors of colorectal cancer progression. This review provides an in-depth analysis of the fusion-fission dynamics and the underlying pathological mechanisms in colorectal cancer cells. Additionally, it offers partial insights into the mitochondrial kinetics in colorectal cancer-associated cells, such as immune and endothelial cells. This review is aimed at identifying key molecular events involved in colorectal cancer progression and highlighting the potential of mitochondrial dynamic proteins as emerging targets for pharmacological intervention. Disruption of the mitochondrial fusion-fission dynamics balance plays a dual role in colorectal cancer development. Mitochondrial fission promotes cancer cell proliferation, invasion, migration, and chemoresistance, while excessive fission induces apoptosis. Similarly, mitochondrial fusion attenuates intestinal epithelial cells from oxidative stress damage, whereas excessive fusion promotes abnormal tumor proliferation and metastasis.image