Examination of the superoxide/hydrogen peroxide forming and quenching potential of mouse liver mitochondria

Slade, Liam; Chalker, Julia; Kuksal, Nidhi; Young, Adrian; Gardiner, Danielle; Mailloux, Ryan J.

doi:10.1016/j.bbagen.2017.05.010

Cited by 50 publications

(62 citation statements)

References 42 publications

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“…In fact, PDH and OGDH have been shown to form ~ 4 × and ~ 8 × more ROS than Complex I in muscle mitochondria . By contrast, our group has shown that OGDH and Complex III are high‐capacity

O_{2}^{\cdot -}

/H 2 O 2 ‐forming sites in liver mitochondria oxidizing pyruvate and malate with PDH making a minor contribution . In the present study, it was observed that sodium formate did not alter succinate‐driven ROS production.…”

Section: Discussioncontrasting

confidence: 70%

“…Indeed, PDH and OGDH produce ~ 4 × and ~ 8 × more ROS than Complex I in muscle mitochondria . It has also been found that OGDH is a major source of ROS in liver mitochondria, whereas PDH makes a minor contribution . Using site‐specific inhibitors for PDH and OGDH, we tested whether either enzyme complex could account for the formate‐induced increase in mitochondrial ROS production.…”

Section: Resultsmentioning

confidence: 99%

“…Similar observations were made with CPI‐613 except it only inhibited ROS production by ~ 60% in control mitochondria, whereas a ~ 75% decrease was observed with mitochondria supplemented with sodium formate. Our group recently showed that ~ 150 μ m CPI‐613 and at least 1 m m KMV was required to induce maximal inhibition (~ 90%) of pyruvate‐driven ROS production in liver mitochondria and that both compounds are equally effective at limiting

O_{2}^{\cdot -}

/H 2 O 2 .…”

Section: Resultsmentioning

confidence: 99%

“…We also found that KMV, a structural analog for 2‐oxoglutarate, and CPI‐613, a lipoic acid analog and putative PDH and OGDH inhibitor, induced an ~ 80% decrease in ROS emission from mitochondria supplemented with sodium formate. It was previously found that Complex III accounts for ~ 45% of the total ROS emitted from mitochondria metabolizing pyruvate and malate, whereas OGDH contributed ~ 30% . PDH and other sources like Complex I made up the remaining ~ 15%.…”

Section: Discussionmentioning

confidence: 99%

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Physiological levels of formate activate mitochondrial superoxide/hydrogen peroxide release from mouse liver mitochondria

et al. 2017

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Here, we found that formate, an essential one-carbon metabolite, activates superoxide (O2·-)/hydrogen peroxide (H O ) release from mitochondria. Sodium formate (30 μm) induces a significant increase in O2·-/H O production in liver mitochondria metabolizing pyruvate (50 μm). At concentrations deemed to be toxic, formate does not increase O2·-/H O production further. It was observed that the formate-mediated increase in O2·-/H O production is not associated with cytochrome c oxidase (COX) inhibition or changes in membrane potential and NAD(P)H levels. Sodium formate supplementation increases phosphorylating respiration without altering proton leaks. Finally, it was observed that the 2-oxoglutarate dehydrogenase (OGDH) inhibitors 3-methyl-2-oxovaleric acid (KMV) and CPI-613 inhibit the formate-induced increase in pyruvate-driven ROS production. The importance of these findings in one-carbon metabolism and physiology are discussed herein.

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“…In fact, PDH and OGDH have been shown to form ~ 4 × and ~ 8 × more ROS than Complex I in muscle mitochondria . By contrast, our group has shown that OGDH and Complex III are high‐capacity

O_{2}^{\cdot -}

Section: Discussioncontrasting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

O_{2}^{\cdot -}

/H 2 O 2 .…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Physiological levels of formate activate mitochondrial superoxide/hydrogen peroxide release from mouse liver mitochondria

et al. 2017

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“…13 Cellular • O 2¯i s produced by intracellular or cell membrane-residing enzyme complexes (NADPH oxidases, NOX), which reduce O 2 by a 1e¯transfer. Additionally, • O 2c an be a product of pathways localized in mitochondria, [14][15][16][17][18][19][20][21] in other organelles or the cytoplasm. 22 • O 2¯i s rapidly dismutated to H 2 O 2 and O 2 .…”

Section: Redox Chemistry Of Hydrogen Peroxidementioning

confidence: 99%

Review—Quantification of Hydrogen Peroxide by Electrochemical Methods and Electron Spin Resonance Spectroscopy

Gulaboski

Mirčeski

Kappl

et al. 2019

J. Electrochem. Soc.

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Reactive oxygen species (ROS) exhibit different spatial and temporal distributions as well as concentrations in-and outside the cell, thereby functioning as signaling or pathogen-destroying molecules. Especially the ROS H 2 O 2 is important for the patho/physiological status of an organism. Electrochemistry (EM) and electron spin resonance (ESR)-based techniques allow quantification of H 2 O 2 in artificial and living systems, coping a concentration range from low nM up to mM. Working electrodes for EM are optimized by diverse modifications and, additionally, redox mediators are used. Ultramicroelectrodes allow scanning of single cells to spatially resolve and quantify extracellular H 2 O 2 in real-time. With ESR spectroscopy, • O 2¯, but not H 2 O 2 , can be directly determined by spin probes in-and outside of cells in suspensions. Monitoring H 2 O 2 requires formation of intermediate radicals, detectable with spin probes. Low μM [H 2 O 2 ] can thus be assessed specifically. Using suitable spin traps, in-vivo ESR and immuno-spin trapping can visualize different radicals at their respective production sites in small animals, organs and tissues. Here, the redox reaction cascades may interfere with cell metabolism. Optimization of all methods established for H 2 O 2 determination would be favorable to finally combine them for mutual validation. Thus, a deeper insight into cellular ROS metabolism can be obtained.

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Cysteine Switches and the Regulation of Mitochondrial Bioenergetics and ROS Production

Mailloux¹

2019

Mitochondria in Health and in Sickness

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Examination of the superoxide/hydrogen peroxide forming and quenching potential of mouse liver mitochondria

Cited by 50 publications

References 42 publications

Physiological levels of formate activate mitochondrial superoxide/hydrogen peroxide release from mouse liver mitochondria

Physiological levels of formate activate mitochondrial superoxide/hydrogen peroxide release from mouse liver mitochondria

Review—Quantification of Hydrogen Peroxide by Electrochemical Methods and Electron Spin Resonance Spectroscopy

Cysteine Switches and the Regulation of Mitochondrial Bioenergetics and ROS Production

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