11/13/2023 0 Comments Drp1 fission13 AMPK is not only an important detector of energy levels but is also a negative moderator of glycolysis. 5 Drp1 is phosphorylated by specific kinases and signaling pathways during mitochondrial fission, including phosphoglycerate mutase family member 5, 6 AMPK, 7– 9 MAPK, 10– 12, and cyclin-dependent kinase 1/cyclin B1 (Cdk1/cyclin B1). However, Ser637 phosphorylation reverses this process. 4 Accumulating evidence indicates that Ser616 phosphorylation promotes the translocation of Drp1 from the cytosol to the mitochondrial outer membrane. 3 Strikingly, phosphorylation of Drp1 plays a crucial role in Drp1 activity regulation. The contribution of active Drp1 is one of the important factors that affect the function of mitochondria. 2 Drp1 is required for mitochondrial fission and acts as a protein marker for mitochondrial dynamics. The proteins that participate in fission and fusion regulation are deemed “mitochondria-shaping” proteins, including dynamin-related protein 1 (Drp1), and mitofusins 1 and 2 (Mfn1 and Mfn2, respectively). 1 Mitochondrial dynamics are equilibrated by the opposing processes of fission and fusion in response to the microenvironment. Dysregulation of mitochondria is closely related to tumor initiation and progression. Mitochondria are multifunctional organelles and perform functions, including regulation of cell bioenergetics, calcium homeostasis, reduction-oxidation balance, and programmed cell death. Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC. Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637. In addition, EBV-LMP1 regulates Drp1 through two oncogenic signaling axes, AMPK and cyclin B1/Cdk1, which promote cell survival and cisplatin resistance in NPC. Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells. Furthermore, the protein level of p-Drp1 (Ser616) is related to the clinical stage (TNM stage) of NPC. A high level of p-Drp1 (Ser616) or a low level of p-Drp1 (Ser637) correlates with poor overall survival and disease-free survival. We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1. The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma (NPC) was determined in our study. However, the mechanism by which oncogenic stress promotes mitochondrial fission, potentially contributing to tumorigenesis, is not entirely understood. Mitochondrial dynamin-related protein 1 (Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers. Recently, mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis. Latent membrane protein 1 (LMP1) is a major Epstein–Barr virus (EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival.
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