Superoxide Flashes

Ma, Qi; Fang, Huaqiang; Wang, Shang; Liu, Lei; Xu, Zhengshuang; Tao, Ye; Wang, Xianhua; Zheng, Ming; Chen, Quan; Cheng, Heping

doi:10.1074/jbc.m111.241794

Cited by 111 publications

(65 citation statements)

References 48 publications

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“…By integrating our findings with those of others (29, 49, 50, 51), we propose that dynamic mitochondrial ROS generation in the form of mPTP-dependent SO flashes serves as a signaling mechanism that controls the fate of NPCs. Our findings suggest that there is considerable complexity and specificity regarding the subcellular localization and temporal coding of ROS generation, and the molecular targets/mechanisms of action of ROS in regulating NPC fate.…”

Section: Discussionsupporting

confidence: 80%

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

et al. 2012

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Although high amounts of reactive oxygen species (ROS) can damage cells, ROS can also play roles as second messengers, regulating diverse cellular processes. Here we report that embryonic mouse cerebral cortical neural progenitor cells (NPCs) exhibit intermittent spontaneous bursts of mitochondrial superoxide (SO) generation (mitochondrial SO flashes) that require transient opening of membrane permeability transition pores (mPTP). This quantal SO production negatively regulates NPC self-renewal. Mitochondrial SO scavengers and mPTP inhibitors reduce SO flash frequency and enhance NPC proliferation, whereas prolonged mPTP opening and SO generation increase SO flash incidence and decrease NPC proliferation. The inhibition of NPC proliferation by mitochondrial SO involves suppression of extracellular signal-regulated kinases. Moreover, mice lacking SOD2 (SOD2−/− mice) exhibit significantly fewer proliferative NPCs and differentiated neurons in the embryonic cerebral cortex at mid-gestation compared with wild type littermates. Cultured SOD2−/− NPCs exhibit a significant increase in SO flash frequency and reduced NPC proliferation. Taken together, our findings suggest that mitochondrial SO flashes negatively regulate NPC self-renewal in the developing cerebral cortex.

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Section: Discussionsupporting

confidence: 80%

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

et al. 2012

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“…The ability to form selenide anion and generate superoxide via oxidation of GSH and other thiols was shown in vitro mainly for selenite, selenium dioxide, selenocystine and selenocystamine but not for elemental selenium, selenate, selenomethionine, selenoethionine and other not active compounds as shown by laboratory studies of Spallholz et al and others [112]. The ability to produce ROS explains dose dependent toxic effects of Se, observed in vitro and in vivo [108] and is considered to underlie its genotoxic [113,114] and proapoptotic activity [115][116][117]. However, some of these dose dependent effects, specifically DNA damage and apoptosis, were observed in vivo after treatment with SeMet, which is a Se compound regarded as nontoxic due to the inability to generate ROS [118][119][120].…”

Section: Biochemical Evidencementioning

confidence: 88%

Selenium and Human Health: Witnessing a Copernican Revolution?

Jabłońska

Vinceti

2015

Journal of Environmental Science and Health, Part C

134

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In humans, selenium was hypothesized to lower the risk of several chronic diseases, mainly due to the antioxidant activity of selenium-containing proteins. Recent epidemiologic and laboratory Downloaded by [New York University] at 16:24 19 June 2015 ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT 2studies, however, are changing our perception of the biological effects of this nutritionally essential trace element. We reviewed the most recent epidemiologic and biochemical literature on selenium, synthesizing the findings from these studies into a unifying view. Randomized trials have shown that selenium did not protect against cancer and other chronic diseases, but even increased the risk of specific neoplasms such as advanced prostate cancer and skin cancer, in addition to type 2 diabetes. Biochemical studies indicate that selenium may exert a broad pattern of toxic effects at unexpectedly low concentrations. Furthermore, its upregulation of antioxidant proteins (selenium-dependent and selenium-independent) may be a manifestation of self-induced oxidative stress. In conclusion, toxic effects of selenium species occur at lower concentrations than previously believed. Those effects may include a large range of proteomic changes and adverse health effects in humans. Since the effects of environmental exposure to this element on human health still remain partially unknown, but are potentially serious, the toxicity of selenium exposure should be further investigated and considered as a public health priority.

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“…These arguments have been countered by data suggesting a correlation of ‘mitoflashes’ with the response of chemical ROS probes 11-13 , the notion that the pH probe SypHer may also respond to superoxide 17 , and the suggestion that a ‘mitoflash’ represents a mixture of superoxide burst and pH transient 11,13 . Ultimate resolution of the debate has been hampered by the use of different biological systems and the complexity of mitochondrial physiology, where matrix pH and free radical release are connected via the electron transport chain and linked to several other parameters such as availability of respiratory substrates, membrane potential, redox and ion homeostasis, and mitochondrial morphology 2,5-7,10,14-16 . Here we resolve the controversy by a thorough analysis of the fundamental properties of the ‘mitoflash’ sensor cpYFP.…”

mentioning

confidence: 99%

The ‘mitoflash’ probe cpYFP does not respond to superoxide

Schwarzländer

Wagner

Ermakova

et al. 2014

Nature

113

100

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Ageing and lifespan of organisms are determined by complicated interactions between their genetics and the environment, but the cellular mechanisms remain controversial. There have been a number of studies suggesting that cellular energy metabolism and free radical dynamics affect lifespan, implicating mitochondrial function. Recently, Shen et al.1 provided apparent mechanistic insight by reporting that mitochondrial oscillations of ‘free radical production’, called ‘mitoflashes’, in the pharynx of 3-day old Caenorhabditis elegans correlated inversely with lifespan. The interpretation of ‘mitoflashes’ as ‘bursts of superoxide’ radicals assumes that circularly permuted yellow fluorescent protein (cpYFP) is a reliable indicator of mitochondrial superoxide2. This interpretation has been criticised because experiments and theoretical considerations both show that changes in cpYFP fluorescence are due to alterations in pH, not superoxide3-7. We now provide direct evidence that purified cpYFP is completely unresponsive to superoxide. Therefore ‘mitoflashes’ do not reflect superoxide generation and are not evidence for a link between mitochondrial free radical dynamics and lifespan.

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Superoxide Flashes

Cited by 111 publications

References 48 publications

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

Mitochondrial Superoxide Production Negatively Regulates Neural Progenitor Proliferation and Cerebral Cortical Development

Selenium and Human Health: Witnessing a Copernican Revolution?

The ‘mitoflash’ probe cpYFP does not respond to superoxide

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