Redox Homeostasis and Mitochondrial Dynamics

Willems, Peter H.G.M.; Rossignol, Rodrigue; Dieteren, Cindy E.; Murphy, Michael P.; Koopman, Werner J.H.

doi:10.1016/j.cmet.2015.06.006

Cited by 568 publications

(430 citation statements)

References 120 publications

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“…The changes may have been caused by changes in mitochondrial fusion and/or fission and its movement, suggesting that the chemical alters mitochondrial dynamics. Mitochondrial morphology and dynamics are interlinked with cellular and mitochondrial redox homeostasis [51] . Cells deficient in mitochondrial fusion proteins (Mfn1, Mfn2, or Opa1) display a fragmented mitochondrial morphology and increased ROS levels and then die.…”

Section: Discussionmentioning

confidence: 99%

“…Cells deficient in mitochondrial fusion proteins (Mfn1, Mfn2, or Opa1) display a fragmented mitochondrial morphology and increased ROS levels and then die. Conversely, chemical or genetic inhibitions of mitochondrial fission proteins (Drp1 or Fis) induce mitochondrial elongation and reduce ROS production [51,52] . Thus, mitochondrial fragmentation allows increases in ROS production.…”

Section: Discussionmentioning

confidence: 99%

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The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

et al. 2017

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Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a well-known polyphenol that is present in grapes, peanuts, pine seeds, and several other plants. Resveratrol exerts deleterious effects on various types of human cancer cells. Here, we analyzed the cell death-inducing mechanisms of resveratrol-006 (Res-006), a novel resveratrol derivative in human liver cancer cells in vitro. Res-006 suppressed the viability of HepG2 human hepatoma cells more effectively than resveratrol (the IC 50 values were 67.2 and 354.8 μmol/L, respectively). Co-treatment with the ER stress regulator 4-phenylbutyrate (0.5 mmol/L) or the ROS inhibitor N-acetyl-L-cysteine (NAC, 1 mmol/L) significantly attenuated Res-006-induced HepG2 cell death, suggesting that pro-apoptotic ER stress and/or ROS may govern the Res-006-induced HepG2 cell death. We further revealed that treatment of HepG2 cells with Res-006 (65 μmol/L) immediately elicited the dysregulation of mitochondrial dynamics and the accumulation of mitochondrial ROS. It also collapsed the mitochondrial membrane potential and further induced ER stress and cell death. These events, except for the change in mitochondrial morphology, were prevented by the exposure of the HepG2 cells to the mitochondrial ROS scavenger, Mito-TEMPO (300-1000 μmol/L). The results suggest that Res-006 may kill HepG2 cells through cell death pathways, including the ER stress initiated by mitochondrial ROS accumulation. The cell death induced by this novel resveratrol derivative involves crosstalk between the mitochondria and ER stress mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

et al. 2017

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“…79 Fusion, and the consequent sharing of antioxidant defense, is considered a protective response to oxidative stress, preserving mitochondrial redox balance. 78,80 Indeed, mitochondrial fragmentation is associated with increased mitochondrial ROS levels, conversely tubular morphology prevents ROS production. 51,80 A549.B2 cells, but not RD.Myo cells, are equipped with robust antioxidant defenses 81 that maintain redox homeostasis and may protect them from the oxidative stress arisen by mitochondrial fragmentation (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

et al. 2016

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Pathological mutations in the mitochondrial DNA (mtDNA) produce a diverse range of tissue-specific diseases and the proportion of mutant mitochondrial DNA can increase or decrease with time via segregation, dependent on the cell or tissue type. Previously we found that adenocarcinoma (A549.B2) cells favored wild-type (WT) mtDNA, whereas rhabdomyosarcoma (RD.Myo) cells favored mutant (m3243G) mtDNA. Mitochondrial quality control (mtQC) can purge the cells of dysfunctional mitochondria via mitochondrial dynamics and mitophagy and appears to offer the perfect solution to the human diseases caused by mutant mtDNA. In A549.B2 and RD.Myo cybrids, with various mutant mtDNA levels, mtQC was explored together with macroautophagy/autophagy and bioenergetic profile. The 2 types of tumor-derived cell lines differed in bioenergetic profile and mitophagy, but not in autophagy. A549.B2 cybrids displayed upregulation of mitophagy, increased mtDNA removal, mitochondrial fragmentation and mitochondrial depolarization on incubation with oligomycin, parameters that correlated with mutant load. Conversely, heteroplasmic RD.Myo lines had lower mitophagic markers that negatively correlated with mutant load, combined with a fully polarized and highly fused mitochondrial network. These findings indicate that pathological mutant mitochondrial DNA can modulate mitochondrial dynamics and mitophagy in a cell-type dependent manner and thereby offer an explanation for the persistence and accumulation of deleterious variants.

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“…Finally, accumulated ROS (and reactive nitrogen species, RNS) are able, in turn, to modify either directly or indirectly several mitochondriashaping proteins, thus creating a positive feedback loop [110,111].…”

Section: Mitochondrial Dynamics and Ros Production In Cancermentioning

confidence: 99%

The mitochondrial dynamics in cancer and immune-surveillance

Simula

Nazio

Campello

2017

Seminars in Cancer Biology

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A B S T R A C TMitochondria-shaping proteins control the dynamic equilibrium between fusion and fission of the mitochondrial network. Their balance is strictly required to regulate various processes, including the quality of mitochondria, cell metabolism, cell death, proliferation and cell migration. Alterations in these processes are frequently encountered in cancer, during both its onset and later progression, as evidence emerge connecting alterations in mitochondrial dynamics with cancer development. In recent years, novel therapeutic approaches to fight against different human tumors aim at exploiting the immune system's ability to specifically recognize tumor antigens, thus killing malignant cells in a process named immune-surveillance. Interestingly, data are accumulating on the role that mitochondrial dynamics play also for the correct function of both the innate and the adaptive immune system. By this review, we overview how mitochondrial dynamics can affect various processes during cancer development, acting directly on tumor cells or indirectly on cells responsible for tumor aggression and defence.

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Redox Homeostasis and Mitochondrial Dynamics

Cited by 568 publications

References 120 publications

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

The novel resveratrol derivative 3,5-diethoxy-3′,4′-dihydroxy-trans-stilbene induces mitochondrial ROS-mediated ER stress and cell death in human hepatoma cells in vitro

Mitochondrial quality control: Cell-type-dependent responses to pathological mutant mitochondrial DNA

The mitochondrial dynamics in cancer and immune-surveillance

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