Manganese superoxide dismutase in carcinogenesis: friend or foe?

Konzack, Anja; Kietzmann, Thomas

doi:10.1042/bst20140076

Cited by 14 publications

(10 citation statements)

References 43 publications

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“…Superoxide dismutase (SOD) 2 is responsible for the dismutation of O 2 2 to H 2 O 2 /O 2 and inhibition of oxidative signals in mitochondria. Loss of SOD 2 causes an increase in mROS, a decrease in the mitochondrial membrane potential, and impaired oxidative phosphorylation (58). As shown in Fig.…”

Section: Reduction Of Mitochondrial Membrane Potential and Mitochondrmentioning

confidence: 84%

Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress

Zhang

Wang

et al. 2018

The Journal of Immunology

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Mature naive T cells circulate through the secondary lymphoid organs in an actively enforced quiescent state. Impaired cell survival and cell functions could be found when T cells have defects in quiescence. One of the key features of T cell quiescence is low basal metabolic activity. It remains unclear at which developmental stage T cells acquire this metabolic quiescence. We compared mitochondria among CD4 single-positive (SP) T cells in the thymus, CD4 recent thymic emigrants (RTEs), and mature naive T cells in the periphery. The results demonstrate that RTEs and naive T cells had reduced mitochondrial content and mitochondrial reactive oxygen species when compared with SP thymocytes. This downregulation of mitochondria requires T cell egress from the thymus and occurs early after young T cells enter the circulation. Autophagic clearance of mitochondria, but not mitochondria biogenesis or fission/fusion, contributes to mitochondrial downregulation in RTEs. The enhanced apoptosis signal-regulating kinase 1/MAPKs and reduced mechanistic target of rapamycin activities in RTEs relative to SP thymocytes may be involved in this mitochondrial reduction. These results indicate that the gain of metabolic quiescence is one of the important maturation processes during SP-RTE transition. Together with functional maturation, it promotes the survival and full responsiveness to activating stimuli in young T cells.

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Section: Reduction Of Mitochondrial Membrane Potential and Mitochondrmentioning

confidence: 84%

Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress

Zhang

Wang

et al. 2018

The Journal of Immunology

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“…A third extracellular variant, EcSOD or SOD3, is secreted and forms a glycosylated heterotetramer bound to the extracellular matrix [35] but again the enzyme activity is Cu-, Zn-dependent. Importantly, changes in the cytosolic Cu/ZnSOD (SOD1), mitochondrial MnSOD (SOD2) or extracellular EcSOD (SOD3) activity or expression correlate with ROS levels [36] .…”

Section: Glutathione and Glutathione-related Post-translational Modifmentioning

confidence: 99%

“…Dysfunction or failure in the dismutation process is linked to the pathogenesis of a number of diseases [36] . Thereby the impact and tissue affected by the different SODs seems to vary; SOD1 has been clearly linked to amyotrophic lateral sclerosis, the extracellular superoxide dismutase (SOD3, ecSOD) seems to be involved in hypertension, acute respiratory distress syndrome, or chronic obstructive pulmonary disease [37] and SOD2 has been linked with carcinogenesis [36] . The removal of superoxide anion by superoxide dismutase(s) appears to be important for a number of cellular processes, among them mitochondrial and ER function (see below).…”

Section: Glutathione and Glutathione-related Post-translational Modifmentioning

confidence: 99%

Antioxidant responses and cellular adjustments to oxidative stress

Espinosa‐Díez¹,

Miguel²,

Mennerich³

et al. 2015

Redox Biology

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935

638

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Redox biological reactions are now accepted to bear the Janus faceted feature of promoting both physiological signaling responses and pathophysiological cues. Endogenous antioxidant molecules participate in both scenarios. This review focuses on the role of crucial cellular nucleophiles, such as glutathione, and their capacity to interact with oxidants and to establish networks with other critical enzymes such as peroxiredoxins. We discuss the importance of the Nrf2-Keap1 pathway as an example of a transcriptional antioxidant response and we summarize transcriptional routes related to redox activation. As examples of pathophysiological cellular and tissular settings where antioxidant responses are major players we highlight endoplasmic reticulum stress and ischemia reperfusion. Topologically confined redox-mediated post-translational modifications of thiols are considered important molecular mechanisms mediating many antioxidant responses, whereas redox-sensitive microRNAs have emerged as key players in the posttranscriptional regulation of redox-mediated gene expression. Understanding such mechanisms may provide the basis for antioxidant-based therapeutic interventions in redox-related diseases.

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“…For example, transgenic mice lacking SOD2 suffer severe cardiopulmonary and neurological damage (Misawa et al, 2006; Li et al, 1995). Conversely, SOD2 overactivity has been linked to increased invasiveness of tumor metastasis (Idelchik et al, 2017; Konzack and Kietzmann, 2014; Hemachandra et al, 2015). Since accumulation of superoxide (O 2 •− ) radical, particularly inside the mitochondria, is often considered as an initial step in the pathogenesis of these diseases, the control of SOD2 activity is therefore critical for maintaining the balance between cell survival and proliferation.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Phosphorylation of the C Terminus of Hsp70 Regulates the Mitochondrial Import of SOD2 and Redox Balance

Zemanovic¹,

Иванов

Bhatnagar

et al. 2018

Cell Reports

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SUMMARY The import of superoxide dismutase-2 (SOD2) into mitochondria is vital for the survival of eukaryotic cells. SOD2 is encoded within the nuclear genome and translocated into mitochondria for activation after translation in the cytosol. The molecular chaperone Hsp70 modulates SOD2 activity by promoting import of SOD2 into mitochondria. In turn, the activity of Hsp70 is controlled by co-chaperones, particularly CHIP, which directs Hsp70-bound proteins for degradation in the proteasomes. We investigated the mechanisms controlling the activity of SOD2 to signal activation and maintain mitochondrial redox balance. We demonstrate that Akt1 binds to and phosphorylates the C terminus of Hsp70 on Serine631, which inhibits CHIP-mediated SOD2 degradation thereby stabilizing and promoting SOD2 import. Conversely, increased mitochondrial-H2O2 formation disrupts Akt1-mediated phosphorylation of Hsp70, and non-phosphorylatable Hsp70 mutants decrease SOD2 import, resulting in mitochondrial oxidative stress. Our findings identify Hsp70 phosphorylation as a physiological mechanism essential for regulation of mitochondrial redox balance.

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Manganese superoxide dismutase in carcinogenesis: friend or foe?

Cited by 14 publications

References 43 publications

Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress

Newly Generated CD4+ T Cells Acquire Metabolic Quiescence after Thymic Egress

Antioxidant responses and cellular adjustments to oxidative stress

Dynamic Phosphorylation of the C Terminus of Hsp70 Regulates the Mitochondrial Import of SOD2 and Redox Balance

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