Mitochondrial dynamics in health and disease: mechanisms and potential targets

Mitochondria are organelles that are able to adjust and respond to different stressors and metabolic needs within a cell,showcasing their plasticity and dynamic nature.These abilities allow them to effectively coordinate various cellular functions.Mitochondrial dynamics refers to the changing process of fission,fusion,mitophagy and transport,which is crucial for optimal function in signal transduction and metabolism.An imbalance in mitochondrial dynamics can disrupt mitochondrial function,leading to abnormal cellular fate,and a range of diseases,including neurodegenerative disorders,metabolic diseases,cardiovascular diseases and cancers.Herein,we review the mechanism of mitochondrial dynamics,and its impacts on cellular function.We also delve into the changes that occur in mitochondrial dynamics during health and disease,and offer novel perspectives on how to target the modulation of mitochondrial dynamics.

Inflammation and tumor progression:signaling pathways and targeted intervention

Cancer development and its response to therapy are regulated by inflammation,which either promotes or suppresses tumor progression,potentially displaying opposing effects on therapeutic outcomes.Chronic inflammation facilitates tumor progression and treatment resistance,whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells(DCs)and antigen presentation,leading to anti-tumor immune responses.In addition,multiple signaling pathways,such as nuclear factor kappa B(NF-kB),Janus kinase/signal transducers and activators of transcription(JAK-STAT),toll-like receptor(TLR)pathways,cGAS/STING,and mitogen-activated protein kinase(MAPK);inflammatory factors,including cytokines(e.g.,interleukin(IL),interferon(IFN),and tumor necrosis factor(TNF)-a),chemokines(e.g.,C-C motif chemokine ligands(CCLs)and C-X-C motif chemokine ligands(CXCLs)),growth factors(e.g.,vascular endothelial growth factor(VEGF),transforming growth factor(TGF)-P),and inflammasome;as well as inflammatory metabolites including prostaglandins,leukotrienes,thromboxane,and specialized proresolving mediators(SPM),have been identified as pivotal regulators of the initiation and resolution of inflammation.Nowadays,local irradiation,recombinant cytokines,neutralizing antibodies,small-molecule inhibitors,DC vaccines,oncolytic viruses,TLR agonists,and SPM have been developed to specifically modulate inflammation in cancer therapy,with some of these factors already undergoing clinical trials.Herein,we discuss the initiation and resolution of inflammation,the crosstalk between tumor development and inflammatory processes.We also highlight potential targets for harnessing inflammation in the treatment of cancer.