Modelling mitochondrial ROS production by the respiratory chain

Mazat, Jean‐Pierre; Devin, Anne; Ransac, Stéphane

doi:10.1007/s00018-019-03381-1

Cited by 123 publications

(78 citation statements)

References 83 publications

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“…The use of inhibitors of the mitochondrial respiratory chain such as rotenone and antimycin, as well as the substrates for the various complexes such as pyruvate or succinate, have let to the identification of the different complexes involved. To date, complexes I, II, and III have been identified as production sites for superoxide anions [51,52].…”

Section: Mitochondrial Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Cardiovascular Diseases

et al. 2020

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Reactive oxygen species (ROS) are subcellular messengers in signal transductions pathways with both beneficial and deleterious roles. ROS are generated as a by-product of mitochondrial respiration or metabolism or by specific enzymes such as superoxide dismutases, glutathione peroxidase, catalase, peroxiredoxins, and myeloperoxidases. Under physiological conditions, the low levels of ROS production are equivalent to their detoxification, playing a major role in cellular signaling and function. In pathological situations, particularly atherosclerosis or hypertension, the release of ROS exceeds endogenous antioxidant capacity, leading to cell death. At cardiovascular levels, oxidative stress is highly implicated in myocardial infarction, ischemia/reperfusion, or heart failure. Here, we will first detail the physiological role of low ROS production in the heart and the vessels. Indeed, ROS are able to regulate multiple cardiovascular functions, such as cell proliferation, migration, and death. Second, we will investigate the implication of oxidative stress in cardiovascular diseases. Then, we will focus on ROS produced by NAPDH oxidase or during endothelial or mitochondrial dysfunction. Given the importance of oxidative stress at the cardiovascular level, antioxidant therapies could be a real benefit. In the last part of this review, we will detail the new therapeutic strategies potentially involved in cardiovascular protection and currently under study.

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Section: Mitochondrial Oxidative Stressmentioning

confidence: 99%

Oxidative Stress in Cardiovascular Diseases

et al. 2020

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“…ROS production may stem from lysosomes, mitochondria, and imbalance between cellular oxidants and antioxidants; thus, the possible origin of ROS generation in DpdtC-induced growth inhibition needed to be determined. Generally, the main types of ROS from mitochondria are superoxide and peroxide [44], while the hydroxyl radical is mainly due to Fenton reaction occurred in lysosomes or labile iron pool. In our study, DpdtC caused marked decrease of ferritin, accompanied by increasing of NCOA4 and autophagy- related proteins, revealing that the ROS production partly stemmed from the occurrence of ferritinophagy (Figures 2, 3, and S2), in accordance with observation in HepG2 cells reported previously [38].…”

Section: Discussionmentioning

confidence: 99%

DpdtC-Induced EMT Inhibition in MGC-803 Cells Was Partly through Ferritinophagy-Mediated ROS/p53 Pathway

Feng

et al. 2020

Oxidative Medicine and Cellular Longevity

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Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells are partially transformed into stromal cells, which endows the polarized epithelium cells more invasive feature and contributes cancer metastasis and drug resistance. Ferritinophagy is an event of ferritin degradation in lysosomes, which contributes Fenton-mediated ROS production. In addition, some studies have shown that ROS participates in EMT process, but the effect of ROS stemmed from ferritin degradation on EMT has not been fully established. A novel iron chelator, DpdtC (2,2′-di-pyridylketone dithiocarbamate), which could induce ferritinophagy in HepG2 cell in our previous study, was used to investigate its effect on EMT in gastric cancer cells. The proliferation assay showed that DpdtC treatment resulted in growth inhibition and morphologic alteration in MGC-803 cell (IC50=3.1±0.3 μM), and its action involved ROS production that was due to the occurrence of ferritinophagy. More interestingly, DpdtC could also inhibit EMT, leading to the upregulation of E-cadherin and the downregulation of vimentin; however, the addition of NAC and 3-MA could attenuate (or neutralize) the action of DpdtC on ferritinophagy induction and EMT inhibition, supporting that the enhanced ferritinophagic flux contributed to the EMT inhibition. Since the degradation of ferritin may trigger the production of ROS and induce the response of p53, we next studied the role of p53 in the above two-cell events. As expected, an upregulation of p53 was observed after DpdtC insulting; however, the addition of a p53 inhibitor, PFT-α, could significantly attenuate the action of DpdtC on ferritinophagy induction and EMT inhibition. In addition, autophagy inhibitors or NAC could counteract the effect of DpdtC and restore the level of p53 to the control group, indicating that the upregulation of p53 was caused by ferritinophagy-mediated ROS production. In conclusion, our data demonstrated that the inhibition of EMT induced by DpdtC was realized through ferritinophagy-mediated ROS/p53 pathway, which supported that the activation of ferritinophagic flux was the main driving force in EMT inhibition in gastric cancer cells, and further strengthening the concept that NCOA4 participates in EMT process.

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“…The general idea of the interplay between depolarization of the mitochondrial membrane and ROS production is that, upon mitochondrial damage or dysfunction, mitochondrial pores open and allowing the in ux of potassium and calcium cations, thereby depolarizing the mitochondrial membrane, which in turn induces ROS production and release. Meanwhile, excessive ROS directly causing the collapse of MMP and depletion of ATP, which later activates a series of signaling pathways that induce apoptosis [29]. Several studies showed prohibitin acts as a coactivator for ARE-dependent gene expression and promotes endogenous antioxidant defense components under oxidative stress [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Prohibitin Protects Against Cigarette Smoke Extract-Induced Cell Apoptosis in Cultured Human Pulmonary Microvascular Endothelial Cells

Peng

Zhou

et al. 2020

Preprint

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Prohibitin is an evolutionarily conserved and ubiquitously expressed protein in eukaryocyte. It mediate many important roles in cell survival, apoptosis, autophagy and senescence. In the present study, we aimed to explore the role of prohibitin in cigarette smoke extract (CSE)-induced apoptosis of human pulmonary microvascular endothelial cells (HPMECs). For this purpose, HPMECs were trasfected with prohibitin and challenged with CSE. Our results showed that CSE exposure inhibited prohibitin expression in a dose-dependent manner in HPMECs. Overexpression of prohibitin could protect cell from CSE-induced injury by inhibiting CSE-induced cell apoptosis, inhibiting reactive oxygen species (ROS) production, increase mitochondrial membrane potential, increase the content of mitochondrial transcription factor A (mtTFA), IKKα/β phosphorylation and IκB-α degradation. CSE decreases prohibitin expression in endothelial cells and restoration of prohibitin expression in these cells can protect against the deleterious effects of CSE on mitochondrial and cells. We identified prohibitin is a novel regulator of endothelial cell apoptosis and survival in the context of cigarette smoke exposure.

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Modelling mitochondrial ROS production by the respiratory chain

Cited by 123 publications

References 83 publications

Oxidative Stress in Cardiovascular Diseases

Oxidative Stress in Cardiovascular Diseases

DpdtC-Induced EMT Inhibition in MGC-803 Cells Was Partly through Ferritinophagy-Mediated ROS/p53 Pathway

Prohibitin Protects Against Cigarette Smoke Extract-Induced Cell Apoptosis in Cultured Human Pulmonary Microvascular Endothelial Cells

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