Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics

Mailloux, Ryan J.; McBride, Skye; Harper, Mary‐Ellen

doi:10.1016/j.tibs.2013.09.001

Cited by 264 publications

(242 citation statements)

References 112 publications

Supporting

Mentioning

237

Contrasting

Unclassified

Order By: Relevance

“…It is also known that many if not all of the abiotic stresses, including temperature, hypoxia, osmotic and pH stress, increase the production of reactive oxygen and nitrogen species (ROS and RNS), in part causing damage to macromolecular cellular structures (Halliwell and Gutteridge, 2007). The cellular sources of ROS during stressful and nonstressful conditions depend on the tissue, but generally involve the mitochondria, endoplasmic reticulum (ER) and peroxisome (Csala et al, 2010;Mailloux et al, 2013;Murphy, 2009;Nordgren and Fransen, 2014).…”

Section: Introductionmentioning

confidence: 99%

Proteomic responses to environmentally induced oxidative stress

Tomanek

2015

Journal of Experimental Biology

140

132

View full text Add to dashboard Cite

Environmental (acute and chronic temperature, osmotic, hypoxic and pH) stress challenges the cellular redox balance and can lead to the increased production of reactive oxygen species (ROS). This review provides an overview of the reactions producing and scavenging ROS in the mitochondria, endoplasmic reticulum (ER) and peroxisome. It then compares these reactions with the findings of a number of studies investigating the proteomic responses of marine organisms to environmentally induced oxidative stress. These responses indicate that the thioredoxin-peroxiredoxin system is possibly more frequently recruited to scavenge H 2 O 2 than the glutathione system. Isoforms of superoxide dismutase (SOD) are not ubiquitously induced in parallel, suggesting that SOD scavenging activity is sometimes sufficient. The glutathione system plays an important role in some organisms and probably also contributes to protecting protein thiols during environmental stress. Synthesis pathways of cysteine and selenocysteine, building blocks for glutathione and glutathione peroxidase, also play an important role in scavenging ROS during stress. The increased abundance of glutaredoxin and DyP-type peroxidase suggests a need for regulating the deglutathionylation of proteins and scavenging of peroxynitrite. Reducing equivalents for these scavenging reactions are generated by proteins of the pentose phosphate pathway and by NADP-dependent isocitrate dehydrogenase. Furthermore, proteins representing reactions of the tricarboxylic acid cycle and the electron transport system generating NADH and ROS, including those of complex I, II and III, are frequently reduced in abundance with stress. Protein maturation in the ER likely represents another source of ROS during environmental stress, as indicated by simultaneous changes in ER chaperones and antioxidant proteins. Although there are still too few proteomic analyses of non-model organisms exposed to environmental stress for a general pattern to emerge, hyposaline and low pH stress show different responses from temperature and hypoxic stress. Furthermore, comparisons of closely related congeners differing in stress tolerance start to provide insights into biochemical processes contributing to adaptive differences, but more of these comparisons are needed to draw general conclusions. To fully take advantage of a systems approach, studies with longer time courses, including several tissues and more species comparisons are needed.

show abstract

Section: Introductionmentioning

confidence: 99%

Proteomic responses to environmentally induced oxidative stress

Tomanek

2015

Journal of Experimental Biology

140

132

View full text Add to dashboard Cite

show abstract

“…Taurine deficiency can result in mitochondrial oxidative stress in vitro [45], and rotifer-fed cod larvae have abnormal mitochondria in liver and intestinal cells (Elin Kjørsvik, personal communication). We found that many genes important for maintaining the mitochondrial redox environment -nrf2, gpx1, sod2, prdx3, prdx5 and msrb2 [19,46,47] -were differentially regulated in rotifer-fed larvae. The mitochondria are a major site of cellular ROS production, metabolism, and cellular redox signalling molecules [46,48,49].…”

Section: A Rotifer Diet Disrupts Glutathione Homeostasis and Redox Pomentioning

confidence: 87%

“…We found that many genes important for maintaining the mitochondrial redox environment -nrf2, gpx1, sod2, prdx3, prdx5 and msrb2 [19,46,47] -were differentially regulated in rotifer-fed larvae. The mitochondria are a major site of cellular ROS production, metabolism, and cellular redox signalling molecules [46,48,49]. Thus, we suggest ROS induced changes in the mitochondria due to taurine deficiency in rotifer-fed larvae may have a downstream effect that contributes to redox system dysregulation throughout the cell and that this could be one of the factors underlying the inferior growth in rotifer fed fish larvae.…”

Section: A Rotifer Diet Disrupts Glutathione Homeostasis and Redox Pomentioning

confidence: 87%

Diet affects the redox system in developing Atlantic cod (Gadus morhua) larvae

Hamre¹,

Penglase²,

Edvardsen

et al. 2015

Free Radical Biology and Medicine

View full text Add to dashboard Cite

a b s t r a c tThe growth and development of marine fish larvae fed copepods is superior to those fed rotifers, but the underlying molecular reasons for this are unclear. In the following study we compared the effects of such diets on redox regulation pathways during development of Atlantic cod (Gadus morhua) larvae. Cod larvae were fed a control diet of copepods or the typical rotifer/Artemia diet commonly used in commercial marine fish hatcheries, from first feeding until after metamorphosis. The oxidised and reduced glutathione levels, the redox potential, and the mRNA expression of 100 genes in redox system pathways were then compared between treatments during larval development. We found that rotifer/Artemia-fed cod larvae had lower levels of oxidised glutathione, a more reduced redox potential, and altered expression of approximately half of the redox system genes when compared to copepod-fed larvae. This rotifer/Artemia diet-induced differential regulation of the redox system was greatest during periods of suboptimal growth. Upregulation of the oxidative stress response transcription factor, nrf2, and NRF2 target genes in rotifer/Artemia fed larvae suggest this diet induced an NRF2-mediated oxidative stress response. Overall, the data demonstrate that nutritional intake plays a role in regulating the redox system in developing fish larvae. This may be a factor in dietary-induced differences observed in larval growth.

show abstract

“…When protein thiol (SH) groups (pKa ~ 8.5) are within a basic environment (such as the mitochondrial matrix) or have their pKa lowered by proximity to positively charged amino acids they deprotonate and are present in their thiolate (S -) form ( Fig. 2B) (Mailloux et al 2013). Protein thiolate groups reversibly react with ROS (H 2 O 2 , HOCl) to form protein sulfinic acid (SOH).…”

Section: Principles Of Intracellular Ros Generation and Removalmentioning

confidence: 99%

“…Abbreviations: Cytb5red, cytochrome b5 reductase; DHOH, dihydroorotate dehydrogenase; Erv1p/Mia40p, redox system that forms disulfide bridges on proteins to be imported by mitochondria; ETF:QO, electron transfer flavoprotein-ubiquinone oxidoreductase; KGDHC, α-ketoglutarate dehydrogenase complex; MAO, monoamine oxidase; mGPDH, mitochondrial glycerol-3-phosphate dehydrogenase; p66shc, 66-kDa src collagen homologue (shc) adaptor protein; PDHG, pyruvate dehydrogenase complex; VDAC, voltage-dependent anion channel. The data for this figure was compiled from: (Giustarini et al 2009;Koopman et al 2010;Marchi et al 2012;Brown and Borutaite 2012;Nathan and Cunningham-Bussel 2013;Woolley et al 2013;Mailloux et al 2013) Reactions of protein thiol (protein-SH) groups leading to reversible S-nitrosilation (protein-SNO), intra or inter-protein disulfide bond formation (SS) or S-glutationylation (protein-SSG). Abbreviations: 4-HNE, 4-hydroxynonenal; α-TOH, α-tocopherol; α-TO • , α-tocopherol radical; Asc •-, ascorbyl radical; AscH -, ascorbate; CAT, catalase; GCL, glutamate cysteine ligase; GPX, glutathione peroxidase; GR, glutathione reductase; GS, glutathione synthase; GSH, glutathione; GSNOR, S-nitrosoglutathione reductase; GSSG, oxidized glutathione; MDA, malondialdehyde; NADPH, reduced nicotinamide adenine dinucleotide phosphate; NOS, nitric oxide synthase; NOHLA, Nω-hydroxy-L-arginine; PRX, peroxiredoxin; RNS, reactive nitrogen species; ROS, reactive oxygen species; SOD, superoxide dismutase; TRX, …”

Section: Figuresmentioning

confidence: 99%

Integrated High-Content Quantification of Intracellular ROS Levels and Mitochondrial Morphofunction

Sieprath

Corne

Willems

et al. 2016

Advances in Anatomy, Embryology and Cell Biology

View full text Add to dashboard Cite

Oxidative stress arises from an imbalance between the production of reactive oxygen species (ROS) and their removal by cellular antioxidant systems. Especially under pathological conditions, mitochondria constitute a relevant source of cellular ROS. These organelles harbor the electron transport chain, bringing electrons in close vicinity to molecular oxygen. Although a full understanding is still lacking, intracellular ROS generation and mitochondrial function are also linked to changes in mitochondrial morphology. To study the intricate relationships between the different factors that govern cellular redox balance in living cells, we have developed a high-content microscopy-based strategy for simultaneous quantification of intracellular ROS levels and mitochondrial morphofunction. Here, we summarize the principles of intracellular ROS generation and removal, and we explain the major considerations for performing quantitative microscopy analyses of ROS and mitochondrial morphofunction in living cells. Next, we describe our workflow and finally, we illustrate that a multiparametric readout enables the unambiguous classification of chemically perturbed cells as well as laminopathy patient cells. Principles of intracellular ROS generation and removalReactive oxygen species (ROS) are small, short-lived derivatives of molecular oxygen (O 2 ) of radical and non-radical nature (Halliwell and Gutteridge 2007 • ), nitrate radical (NO 3 • ) and many other nitrogen derivatives. ROS were originally described as molecular constituents of the defense system of phagocytic cells, but it has become clear that besides their damaging properties, they also function as signaling molecules and mediate a variety of other cellular responses including cell proliferation, differentiation, gene expression and migration (Lambeth 2004;Bartz and Piantadosi 2010). Intracellular ROS metabolismROS can be generated at various sites in the cell (Fig. 1A). This can be either deliberately, e.g. by NADPH oxidases (NOX), or as a byproduct, e.g. during normal cellular respiration in mitochondria (Babior 1999;Turrens 2003;Murphy 2009). The NOX family of NADPH oxidases (NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2) are proteins that transport electrons (e -) from NADPH across biological membranes (plasma or endomembranes) (Bedard and Krause 2007;Dupre-Crochet et al. 2013). The activation mechanisms and tissue distribution of the isoforms differ but they all use O 2 as e --acceptor, producing O 2•-. Through ROS generation, they play a role in many cellular processes including host defense, regulation of gene expression and cell differentiation (Bedard and Krause 2007). Despite their sometimes significant contribution to the global ROS pools, NOX are not the predominant source of intracellular ROS. Mitochondria are considered the major culprit, in particular under pathological conditions. Mitochondrial ROS are generated as a byproduct of the oxidative phosphorylation (OXPHOS, cf. below). Irrespective of its source, ROS production generally sta...

show abstract

Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics

Cited by 264 publications

References 112 publications

Proteomic responses to environmentally induced oxidative stress

Proteomic responses to environmentally induced oxidative stress

Diet affects the redox system in developing Atlantic cod (Gadus morhua) larvae

Integrated High-Content Quantification of Intracellular ROS Levels and Mitochondrial Morphofunction

Contact Info

Product

Resources

About