Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch

Palma, Flávio R.; He, Chenxia; Danes, Jeanne M.; Paviani, Verônica; Coelho, Diego R.; Gantner, Benjamin N.; Bonini, Marcelo G.

doi:10.1089/ars.2019.7962

Cited by 98 publications

(73 citation statements)

References 128 publications

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“…50,51 It is clear that the activity of SOD2 can be regulated through post-translational modifications. 52 For instance, a reduction in SIRT3 decreases the deacetylation of SOD2, resulting in ROS accumulation. 53,54 SIRT3 is the most robust deacetylase and highly expressed in mitochondria that appears to play a crucial role on the regulation of oxidative stress and redox homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Jiang

Liang

Zhang

et al. 2020

Journal of Pineal Research

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Fine particulate matter (PM 2.5) exposure is correlated with the risk of developing cardiac fibrosis. Melatonin is a major secretory product of the pineal gland that has been reported to prevent fibrosis. However, whether melatonin affects the adverse health effects of PM 2.5 exposure has not been investigated. Thus, this study was aimed to investigate the protective effect of melatonin against PM 2.5-accelerated cardiac fibrosis. The echocardiography revealed that PM 2.5 had impaired both systolic and diastolic cardiac function in ApoE-/mice. Histopathological analysis demonstrated that PM 2.5 induced cardiomyocyte hypertrophy and fibrosis, particularly perivascular fibrosis. While the melatonin administration was effective in alleviating PM 2.5-induced cardiac dysfunction and fibrosis in mice. Results of electron microscopy and confocal scanning laser microscope confirmed that melatonin had restorative effects against impaired mitochondrial ultrastructure and augmented mitochondrial ROS generation in PM 2.5-treated group. Further investigation revealed melatonin administration could significantly reverse the PM 2.5-induced phenotypic modulation of cardiac fibroblasts into myofibroblasts. For the first time, our study found that melatonin effectively alleviates PM 2.5-induced cardiac dysfunction and fibrosis via inhibiting mitochondrial oxidative injury and regulating SIRT3-mediated SOD2 deacetylation. Our findings indicate that melatonin could be a therapy medicine for prevention and treatment of air pollution associated cardiac diseases.

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Section: Discussionmentioning

confidence: 99%

Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Jiang

Liang

Zhang

et al. 2020

Journal of Pineal Research

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“…In the current study, mitochondrial superoxide accumulation for both TKIs was observed in both cell models. Mitochondrial ROS was associated with increased mRNA and/or protein expression of SOD2 in both cell models as well as TRX2 protein expression in C2C12 myotubes, which are both located exclusively in mitochondria where they play major roles in ROS scavenging ( Holmgren, 1985 ; Palma et al., 2020 ). Impaired activity of complex I as the main cause for enhanced mitochondrial superoxide accumulation and the increase of the mitochondrial antioxidative defense suggested that both imatinib and dasatinib can cause oxidative stress, which was shown directly by the rise in the mitochondrial superoxide content.…”

Section: Discussionmentioning

confidence: 99%

Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells

et al. 2020

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“…As Imlay [ 220 ] calculates, even picomolar (10 −11/12 M) levels of superoxide are sufficient to inactivate enzymes iron-sulfur proteins like aconitase, with a half-time of ~20 min in E. coli . By controlling the fate of superoxide, MnSOD exerts considerable control over the type of oxidative stress experienced [ 222 ], especially since, in the absence of an anion channel, superoxide will be retained in the matrix [ 223 ]. (reaction 11 in 33% yield [ 224 , 225 , 226 ]).…”

Section: A Framework For Interpreting the Role Of Mitochondrial Romentioning

confidence: 99%

“…Redox relays represent an elegant solution wherein antioxidant enzymes transduce redox signals by transferring H 2 O 2 -derived electrons to target proteins (i.e., uncoupling peroxiredoxin 3 from thioredoxin 2). From a conceptual perspective, redox relays challenge the traditional view of antioxidant enzymes: they play a more nuanced role than merely removing ROS [ 222 , 230 , 258 , 261 ]. As Winterbourn enunciates [ 262 ], several parallel mechanisms may contribute (e.g., local inactivation of peroxiredoxins or locally caging H 2 O 2 and the target).…”

Section: A Framework For Interpreting the Role Of Mitochondrial Romentioning

confidence: 99%

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

Cobley

2020

Antioxidants

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The consensus that assisted reproduction technologies (ART), like in vitro fertilization, to induce oxidative stress (i.e., the known) belies how oocyte/zygote mitochondria—a major presumptive oxidative stressor—produce reactive oxygen species (ROS) with ART being unknown. Unravelling how oocyte/zygote mitochondria produce ROS is important for disambiguating the molecular basis of ART-induced oxidative stress and, therefore, to rationally target it (e.g., using site-specific mitochondria-targeted antioxidants). I review the known mechanisms of ROS production in somatic mitochondria to critique how oocyte/zygote mitochondria may produce ROS (i.e., the unknown). Several plausible site- and mode-defined mitochondrial ROS production mechanisms in ART are proposed. For example, complex I catalyzed reverse electron transfer-mediated ROS production is conceivable when oocytes are initially extracted due to at least a 10% increase in molecular dioxygen exposure (i.e., the intriguing). To address the term oxidative stress being used without recourse to the underlying chemistry, I use the species-specific spectrum of biologically feasible reactions to define plausible oxidative stress mechanisms in ART. Intriguingly, mitochondrial ROS-derived redox signals could regulate embryonic development (i.e., their production could be beneficial). Their potential beneficial role raises the clinical challenge of attenuating oxidative damage while simultaneously preserving redox signaling. This discourse sets the stage to unravel how mitochondria produce ROS in ART, and their biological roles from oxidative damage to redox signaling.

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Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch

Cited by 98 publications

References 128 publications

Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

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Mitochondrial Superoxide Dismutase: What the Established, the Intriguing, and the Novel Reveal About a Key Cellular Redox Switch

Cited by 98 publications

References 128 publications

Melatonin ameliorates PM2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Melatonin ameliorates PM2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Imatinib and Dasatinib Provoke Mitochondrial Dysfunction Leading to Oxidative Stress in C2C12 Myotubes and Human RD Cells

Mechanisms of Mitochondrial ROS Production in Assisted Reproduction: The Known, the Unknown, and the Intriguing

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Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis

Melatonin ameliorates PM_2.5‐induced cardiac perivascular fibrosis through regulating mitochondrial redox homeostasis