Intricate role of DRP1 and associated mitochondrial fission signaling in carcinogenesis and cancer progression

Abstract

The process of mitochondrial fission is a major determinant of mitochondrial homeostasis. DRP1 is the chief architect of the mitochondrial fission process, and the DRP1 recruitment to the mitochondrial outer membrane is necessary for the mitochondrial division. DRP1 contributes to cancer progression by promoting cell proliferation, enhancing resistance to therapy, inhibiting apoptosis, suppressing immune responses, and sustaining cancer stem cell heterogeneity and self-renewal. Moreover, DRP1 drives metabolic reprogramming to support enhanced energy production and biosynthesis required for tumor growth and survival. In addition, DRP1-mediated mitochondrial fission also favours NLRP3 inflammasome activation within the tumor microenvironment, which regulates cancer progression. Interestingly, elevated levels of DRP1 expression have been identified as a significant prognostic marker, correlating with poor survival outcomes across multiple cancer types. Many DRP1 inhibitors have been developed for cancer treatment, but more specific and selective agents are needed to improve efficacy and reduce off-target effects. A comprehensive understanding of DRP1's role in cancer cells is essential for developing DRP1 inhibitors, which hold promise as novel anticancer therapies and may enhance the effectiveness of conventional treatments.