Possible Roles of Mitochondrial Dynamics and the Effects of Pharmacological Interventions in Chemoresistant Ovarian Cancer

Kingnate, Chalita; Charoenkwan, Kittipat; Kumfu, Sirinart; Chattipakorn, Nipon

doi:10.1016/j.ebiom.2018.07.026

Cited by 46 publications

(38 citation statements)

References 45 publications

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“…The balance between these opposing events, at every time or cell demand, determines organelle morphology, which acts as an intracellular signal that instructs different metabolic pathways, reflecting the different physiological functions of the cell. For instance, an elongated network sustains oxidative phosphorylation (OXPHOS) for a correct assembly of the electron transport chain (ETC) complexes, and an optimal ATP production, besides diluting the matrix content (38). A fragmented network, instead, promotes aerobic glycolysis and mitophagy or accelerates cell proliferation in response to nutrient excess and cellular dysfunction (38).…”

Section: Mitochondrial Dynamics In Memory T Cells and T Cell Migrationmentioning

confidence: 99%

Recirculation and Residency of T Cells and Tregs: Lessons Learnt in Anacapri

2020

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Location, location, and location": according to this mantra, the place where living beings settle has a key impact on the success of their activities; in turn, the living beings can, in many ways, modify their environment. This idea has now become more and more true for T cells. The ability of T cells to recirculate throughout blood or lymph, or to stably reside in certain tissues, turned out to determine immunity to pathogens, and tumors. If location matters also for human beings, the inspiring environment of Capri Island has contributed to the success of the EFIS-EJI Ruggero Ceppellini Advanced School of Immunology focused on "T cell memory," held in Anacapri from October 12, 2018 to October 15, 2018. In this minireview, we would like to highlight some novel concepts about T cell migration and residency and discuss their implications in relation to recent advances in the field, including the mechanisms regulating compartmentalization and cell cycle entry of T cells during activation, the role of mitochondrial metabolism in T cell movement, and the residency of regulatory T cells.

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Section: Mitochondrial Dynamics In Memory T Cells and T Cell Migrationmentioning

confidence: 99%

Recirculation and Residency of T Cells and Tregs: Lessons Learnt in Anacapri

2020

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“…The GTPase DRP1 promotes mitochondrial fission, and high DRP1 expression is reported in several cancer types. 22,24,26,28 Reducing DRP1 activity is considered as a potential therapeutic approach for cancer. Mdivi-1 (a widely accepted DRP1 inhibitor) induced cancer cell death and decreased tumour size in xenograft models.…”

Section: Discussionmentioning

confidence: 99%

“…25 High expression of DRP1 in cancer may be a potential target for cancer treatment. 4,5,22,24,[26][27][28] Mitochondrial division inhibitor 1 (mdivi-1) is an efficacious inhibitor of mitochondrial division in yeast and was identified from a chemical screen for compounds that alter mitochondrial morphology. 29 Not surprisingly, mdivi-1 has been widely used as a mitochondrial fusion inducer.…”

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confidence: 99%

Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer

et al. 2020

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BACKGROUND: Previous studies suggested that mdivi-1 (mitochondrial division inhibitor), a putative inhibitor of dynamin-related protein (DRP1), decreased cancer cell proliferation through inducing mitochondrial fusion and altering oxygen consumption. However, the metabolic reprogramming underlying the DRP1 inhibition is still unclear in cancer cells. METHODS: To better understand the metabolic effect of DRP1 inhibition, [U-13 C]glucose isotope tracing was employed to assess mdivi-1 effects in several cancer cell lines, DRP1-WT (wild-type) and DRP1-KO (knockout) H460 lung cancer cells and mouse embryonic fibroblasts (MEFs). RESULTS: Mitochondrial staining confirmed that mdivi-1 treatment and DRP1 deficiency induced mitochondrial fusion. Surprisingly, metabolic isotope tracing found that mdivi-1 decreased mitochondrial oxidative metabolism in the lung cancer cell lines H460, A549 and the colon cancer cell line HCT116. [U-13 C]glucose tracing studies also showed that the TCA cycle intermediates had significantly lower enrichment in mdivi-1-treated cells. In comparison, DRP1-WT and DRP1-KO H460 cells had similar oxidative metabolism, which was decreased by mdivi-1 treatment. Furthermore, mdivi-1-mediated effects on oxidative metabolism were independent of mitochondrial fusion. CONCLUSIONS: Our data suggest that, in cancer cells, mdivi-1, a putative inhibitor of DRP1, decreases oxidative metabolism to impair cell proliferation.

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“…Mitochondrial autophagy (mitophagy) maintains mitochondria mass and function by clearing damaged or overloaded mitochondria. Kingnate et al [36] proposed that increased mitochondrial fusion and reduced mitochondrial fission may be one of the mechanisms of cisplatin resistance in ovarian cancer cells. Williams et al [37] suggested that inhibition of mitochondrial fission leads to mitophagy suppression.…”

Section: Mitophagymentioning

confidence: 99%

Insight into the role of p62 in the cisplatin resistant mechanisms of ovarian cancer

Yan

et al. 2020

Cancer Cell Int

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Cisplatin is a platinum-based first-line drug for treating ovarian cancer. However, chemotherapy tolerance has limited the efficacy of cisplatin for ovarian cancer patients. Research has demonstrated that cisplatin causes changes in cell survival and death signaling pathways through its interaction with macromolecules and organelles, which indicates that investigation into the DNA off-target effects of cisplatin may provide critical insights into the mechanisms underlying drug resistance. The multifunctional protein p62 works as a signaling hub in the regulation of pro-survival transcriptional factors NF-κB and Nrf2 and connects autophagy and apoptotic signals, which play important roles in maintaining cell homeostasis. In this review, we discuss the role of p62 in cisplatin resistance by exploring p62-associated signaling pathways based on current studies and our work. Insights into these resistance mechanisms may lead to more effective therapeutic strategies for ovarian cancer by targeting p62.

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Possible Roles of Mitochondrial Dynamics and the Effects of Pharmacological Interventions in Chemoresistant Ovarian Cancer

Cited by 46 publications

References 45 publications

Recirculation and Residency of T Cells and Tregs: Lessons Learnt in Anacapri

Recirculation and Residency of T Cells and Tregs: Lessons Learnt in Anacapri

Mitochondrial division inhibitor (mdivi-1) decreases oxidative metabolism in cancer

Insight into the role of p62 in the cisplatin resistant mechanisms of ovarian cancer

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