Abstract:
:Mitochondria are critical sources of hydrogen peroxide (H2O2), an important secondary messenger in mammalian cells. Recent work has shown that O2•-/H2O2 emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O2•-/H2O2 release rates from cardiac and liver mitochondria isolated from mice deficient for glutaredoxin-2 (GRX2), a matrix-associated thiol oxidoreductase that facilitates the S-glutathionylation and deglutathionylation of proteins. Liver mitochondria isolated from mice heterozygous (GRX2+/-) and homozygous (GRX2-/-) for glutaredoxin-2 displayed a significant decrease in O2•-/H2O2 release when oxidizing pyruvate or 2-oxoglutarate. The genetic deletion of the Grx2 gene was associated with increased protein expression of pyruvate dehydrogenase (PDH) but not 2-oxoglutarate dehydrogenase (OGDH). By contrast, O2•-/H2O2 production was augmented in cardiac mitochondria from GRX2+/- and GRX2-/- mice metabolizing pyruvate or 2-oxoglutarate which was associated with decreased PDH and OGDH protein levels. ROS production was augmented in liver and cardiac mitochondria metabolizing succinate. Inhibitor studies revealed that OGDH and Complex III served as high capacity ROS release sites in liver mitochondria. By contrast, Complex I and Complex III were found to be the chief O2•-/H2O2 emitters in cardiac mitochondria. These findings identify an essential role for GRX2 in regulating O2•-/H2O2 release from mitochondria in liver and cardiac tissue. Our results demonstrate that the GRX2-mediated regulation of O2•-/H2O2 release through the S-glutathionylation of mitochondrial proteins may play an integral role in controlling cellular ROS signaling.
journal_name
Redox Bioljournal_title
Redox biologyauthors
Chalker J,Gardiner D,Kuksal N,Mailloux RJdoi
10.1016/j.redox.2017.12.006subject
Has Abstractpub_date
2018-05-01 00:00:00pages
216-227issn
2213-2317pii
S2213-2317(17)30837-6journal_volume
15pub_type
杂志文章相关文献
Redox Biology文献大全abstract::Gallbladder cancer (GBC) is a highly malignant bile duct cancer with poor prognosis characterized by its insensitivity to chemotherapy. Emerging evidence indicates that cytoprotective antioxidation is involved in drug resistance of various cancers; however, the underlying molecular mechanisms remain obscure. Here, we ...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101149
更新日期:2019-04-01 00:00:00
abstract::Premature senescence, a death escaping pathway for cells experiencing stress, is conducive to aging and cardiovascular diseases. The molecular switch between senescent and apoptotic fate remains, however, poorly recognized. Nrf2 is an important transcription factor orchestrating adaptive response to cellular stress. H...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101304
更新日期:2020-01-01 00:00:00
abstract::Hypertonia is pathognomonic of cerebral palsy (CP), often caused by brain injury before birth. To understand the early driving events of hypertonia, we utilized magnetic resonance imaging (MRI) assessment of early critical brain injury in rabbit fetuses (79% term) that will predict hypertonia after birth following ant...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101407
更新日期:2020-01-01 00:00:00
abstract::Reactive oxygen and nitrogen species (e.g. H2O2, nitric oxide) confer redox regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. In addition, classical regulation of gene expression or activity, including gene transcription to RNA followed by transla...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2015.05.008
更新日期:2015-08-01 00:00:00
abstract::Highly active anti-retrovirus therapy (HAART) has been used to block the progression and symptoms of human immunodeficiency virus infection. Although it decreases morbidity and mortality, clinical use of HAART has also been linked to various adverse effects such as severe cardiomyopathy resulting from compromised mito...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2017.06.011
更新日期:2017-10-01 00:00:00
abstract::Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world. Recent evidence suggests that RPE and photoreceptors have an interconnected metabolism and that mitochondrial damage in RPE is a trigger for degeneration in both RPE and photoreceptors in AMD. To test this hypothesis, this...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101201
更新日期:2019-06-01 00:00:00
abstract::In order to overcome intercellular variability and thereby effectively assess signal propagation in biological networks it is imperative to simultaneously quantify multiple biological observables in single living cells. While fluorescent biosensors have been the tool of choice to monitor the dynamics of protein intera...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.07.023
更新日期:2018-10-01 00:00:00
abstract::Keloids exhibit metabolic reprogramming including enhanced glycolysis and attenuated oxidative phosphorylation. Hypoxia induces a series of protective responses in mammalian cells. However, the metabolic phenotype of keloid fibroblasts under hypoxic conditions remains to be elucidated. The present study aimed to inves...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101815
更新日期:2021-01-01 00:00:00
abstract::Vitamin C deficiency globally affects several hundred million people and has been associated with increased morbidity and mortality in numerous studies. In this study, bioavailability of the oxidized form of vitamin C (l-dehydroascorbic acid or DHA)-commonly found in vitamin C containing food products prone to oxidati...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2015.11.003
更新日期:2016-04-01 00:00:00
abstract::Divalent copper and iron cations have been acknowledged for their catalytic roles in physiological processes critical for homeostasis maintenance. Being redox-active, these metals act as cofactors in the enzymatic reactions of electron transfer. However, under pathophysiological conditions, owing to their high redox p...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101566
更新日期:2020-07-01 00:00:00
abstract::Metabolic control of cellular function is significant in the context of inflammation-induced metabolic dysregulation in immune cells. Generation of reactive oxygen species (ROS) such as hydrogen peroxide and superoxide are one of the critical events that modulate the immune response in neutrophils. When activated, neu...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2016.06.003
更新日期:2016-10-01 00:00:00
abstract::Yeast Sir2 is an NAD-dependent histone deacetylase related to oxidative stress and aging. In a previous study, we showed that Sir2 is regulated by S-glutathionylation of key cysteine residues located at the catalytic domain. Mutation of these residues results in strains with increased resistance to disulfide stress. I...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101229
更新日期:2019-06-01 00:00:00
abstract::Necroptosis has been discovered as a new paradigm of cell death and may play a key role in heart disease and selenium (Se) deficiency. Hence, we detected the specific microRNA (miRNA) in response to Se-deficient heart using microRNAome analysis. For high-throughput sequencing using Se-deficient chicken cardiac tissue,...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2017.11.025
更新日期:2018-05-01 00:00:00
abstract::Bupivacaine is frequently administered for diagnosing and controlling spine-related pain in interventional spine procedures. However, the potential cytotoxic effects of bupivacaine on intervertebral disc (IVD) cells and the underlying molecular mechanisms have not yet been fully established. Here, we showed that bupiv...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.06.010
更新日期:2018-09-01 00:00:00
abstract::Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vas...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2013.12.027
更新日期:2014-01-09 00:00:00
abstract::Injury-induced stenosis is a serious vascular complication. We previously reported that p38α (MAPK14), a redox-regulated p38MAPK family member was a negative regulator of the VSMC contractile phenotype in vitro. Here we evaluated the function of VSMC-MAPK14 in vivo in injury-induced neointima hyperplasia and the under...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101137
更新日期:2019-04-01 00:00:00
abstract::Williamson and colleagues present important data on the effects of MitoQ - an antioxidant compound targeted to mitochondria - on mtDNA damage following exercise. Future studies are needed to elucidate, whether or not the observed prevention of MitoQ on DNA damage is beneficial with regard to functional outcomes in hea...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101732
更新日期:2021-01-01 00:00:00
abstract::Oxidative stress is reported to regulate several apoptotic and necrotic cell death pathways in auditory tissues. Poly(ADP-ribose) polymerase-1 (PARP-1) can be activated under oxidative stress, which is the hallmark of parthanatos. Autophagy, which serves either a pro-survival or pro-death function, can also be stimula...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2017.10.002
更新日期:2018-04-01 00:00:00
abstract::Neutrophils produce a cocktail of oxidative species during the so-called oxidative burst to attack phagocytized bacteria. However, little is known about the neutrophils' redox homeostasis during the oxidative burst and there is currently no consensus about the interplay between oxidative species and cellular signaling...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101344
更新日期:2020-01-01 00:00:00
abstract::Hypoxia triggers a wide range of protective responses in mammalian cells, which are mediated through transcriptional and post-translational mechanisms. Redox signaling in cells by reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) occurs through the reversible oxidation of cysteine thiol groups, resulting ...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2017.05.020
更新日期:2017-10-01 00:00:00
abstract::Oxidative stress plays a major part in the pathogenesis of drug-induced liver injury. Yet, overcoming it with other xenobiotics impose additional risks. In this study, we consider the use of natural-occurring and purified Vitamin E analogs as hepatoprotective agents. Vitamin E is well-known for its intrinsic antioxida...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2015.01.013
更新日期:2015-01-01 00:00:00
abstract::Cell-free heme (CFH) and hemoglobin (Hb) have emerged as distinct mediators of acute injury characterized by inflammation and microcirculatory dysfunction in hemolytic conditions and critical illness. Several reports have shown changes in Hb and CFH in specific pathophysiological settings. Using PBS, plasma from patie...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2016.08.003
更新日期:2016-10-01 00:00:00
abstract::Hypertension is one of the major predisposing factors for neurodegenerative disease characterized with activated renin-angiotensin system (RAS) in both periphery and brain. Vitamin D (VitD) is recently recognized as a pleiotropic hormone with strong neuroprotective properties. While multiple lines of evidence suggest ...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2019.101295
更新日期:2019-09-01 00:00:00
abstract::Neurodegenerative diseases (NDD) such as Alzheimer's (AD) and Parkinson's disease (PD) are distinct clinical entities, however, the aggregation of key neuronal proteins, presumably leading to neuronal demise appears to represent a common mechanism. It has become evident, that advanced glycation end products (AGEs) tri...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2020.101546
更新日期:2020-07-01 00:00:00
abstract::Retinal tissue receives its supply of oxygen from two sources - the retinal and choroidal circulations. Decreases in retinal blood flow occur in the early stages of diabetes, with the eventual development of hypoxia thought to contribute to pathological neovascularization. Oxygen consumption in the retina has been fou...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2014.04.006
更新日期:2014-04-18 00:00:00
abstract::The widespread detection of elevated oxidative stress levels in many medical conditions has led to numerous efforts to design interventions to reduce its effects. Efforts have been wide-ranging, from dietary changes to administration of antioxidants, supplements, e.g., omega-3-fatty acids, and many medications. Howeve...
journal_title:Redox biology
pub_type: 杂志文章,meta分析
doi:10.1016/j.redox.2018.05.003
更新日期:2018-07-01 00:00:00
abstract::The precise molecular events defining the complex role of oxidative stress in the inactivation of the cerebral sodium pump in radical-induced neurodegenerative diseases is yet to be fully clarified and thus still open. Herein we investigated the modulation of the activity of the cerebral transmembrane electrogenic enz...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2014.12.015
更新日期:2015-01-01 00:00:00
abstract::Mitochondria fulfill a number of biological functions which inherently depend on ATP and O2(-•)/H2O2 production. Both ATP and O2(-•)/H2O2 are generated by electron transfer reactions. ATP is the product of oxidative phosphorylation whereas O2(-•) is generated by singlet electron reduction of di-oxygen (O2). O2(-•) is ...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2015.02.001
更新日期:2015-01-01 00:00:00
abstract::Culturing cells and tissues in vitro has provided valuable insights into the molecular mechanisms regulating redox signaling in cells with implications for medicine. However, standard culture techniques maintain mammalian cells in vitro under an artificial physicochemical environment such as ambient air and 5% CO2. Ox...
journal_title:Redox biology
pub_type: 杂志文章,评审
doi:10.1016/j.redox.2014.04.008
更新日期:2014-04-18 00:00:00
abstract::NRF2 is a redox-responsive transcription factor that regulates expression of cytoprotective genes via its interaction with DNA sequences known as antioxidant response elements (AREs). NRF2 activity is induced by oxidative stress, but oxidative stress is not the only context in which NRF2 can be activated. Mutations th...
journal_title:Redox biology
pub_type: 杂志文章
doi:10.1016/j.redox.2018.07.026
更新日期:2018-10-01 00:00:00