The molecular mechanisms of mitochondrial dynamics and mitophagy and their complex association with cancer drug resistance

The development of drug resistance by cancer cells is among the main reasons for cancer treatment failure, greatly limiting the efficacy of chemotherapy, targeted therapy, and immunotherapy. Mitochondria, as the core organelles of cellular energy metabolism, play a key role in the cellular stress response. The dynamic changes in mitochondria, including fusion, fission, and mitophagy, not only regulate cellular energy metabolism and biosynthesis but also affect cell survival and death. Through mitochondrial fusion, fission, and mitophagy, a sufficient number of effective mitochondria are ensured to supply cellular energy, thereby increasing the tolerance of tumor cells to chemotherapeutic drugs and generating drug resistance. Recently, the role of mitochondrial dynamics and mitophagy in cancer drug resistance has gradually gained attention, but their complex structure and function and multiple roles in tumor biology pose challenges for the clinical application of cancer treatment strategies based on it. Therefore, targeting mitochondrial dynamics and mitophagy for cancer drug resistance has attracted increasing attention for various cancer types. In this study, we provide insights into the molecular mechanisms of mitochondrial fusion, fission, and mitophagy and summarize their complex associations with cancer drug resistance through a systematic review of the latest literature.