Abstract
The emergence, in recent decades, of an entirely new area of “Mitochondrial dynamics”, which consists principally of fission and fusion, reflects the recognition that mitochondria play a significant role in human tumorigenesis and response to therapeutics. Proteins that determine mitochondrial dynamics are referred to as “shaping proteins”. Marked heterogeneity has been observed in the response of tumor cells to chemotherapy, which is associated with imbalances in mitochondrial dynamics and function leading to adaptive and acquired resistance to chemotherapeutic agents. Therefore, targeting mitochondria-shaping proteins may prove to be a promising approach to treat chemotherapy resistant cancers. In this review, we summarize the alterations of mitochondrial dynamics in chemotherapeutic processing and the antitumor mechanisms by which chemotherapy drugs synergize with mitochondria-shaping proteins. These might shed light on new biomarkers for better prediction of cancer chemosensitivity and contribute to the exploitation of potent therapeutic strategies for the clinical treatment of cancers.
Highlights
Mitochondria are important dynamic organelles which can remodel morphology and functions, when cells are exposed to severe conditions, such as hypoxia, viral infections, and nutrient deprivation [1, 2]
Several shaping proteins are involved in this process and mainly include fission proteins, such as mitochondrial dynamin-related protein 1 (Drp1) and mitochondrial outer membrane receptor proteins [i.e., mitochondrial fission 1 protein (Fis1), mitochondrial fission factor (Mff), and mitochondrial dynamics protein of 49/51kDa (MiD49/51)], and fusion proteins such as mitofusin1/2 (Mfn1/2) and optic atrophy 1 (OPA1) [6, 7]
We revealed that Epstein-Barr virus latent membrane protein 1 (EBV-EBV encodes oncoprotein latent membrane protein 1 (LMP1)) increases the mitochondrial fission-induced glycolytic metabolic phenotype for nasopharyngeal carcinoma (NPC) cells survival to resist chemotherapy, and phosphorylation of Drp1 Ser616 or dephosphorylation of Drp1Ser637 is essential for LMP1-regulated enhancement of glycolytic metabolism [98]
Summary
Mitochondria are important dynamic organelles which can remodel morphology and functions, when cells are exposed to severe conditions, such as hypoxia, viral infections, and nutrient deprivation [1, 2]. Hypoxia induces an increased expression of Drp1, thereby promoting mitochondrial fission and enhancing the ability of metastatic tumor cells to invade and metastasize in breast cancer. A new reports identified that hypoxia-induced ROS triggers mitochondrial fission by down-regulating phosphorylated Drp1 (Ser637) and Mfn1 expression levels in ovarian cancer cells, thereby inducing cisplatin resistance [82].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
