The Tricarboxylic Acid Cycle at the Crossroad Between Cancer and Immunity.

Abstract:

: Significance: The tricarboxylic acid (TCA) cycle is a housekeeping metabolic pathway essential for generation of energy and biosynthetic intermediates. Alterations of the TCA cycle play a pivotal role in oncogenesis and inflammation. As such, some metabolic vulnerabilities, imposed by TCA cycle dysfunction in cancer, have been identified. Similarly, the TCA cycle appeared as an actionable pathway in immunopathologies. Recent Advances: Metabolic changes accompanying cell transformation have been usually considered as adaptive mechanisms to malignant transformation. The identification of oncogenic mutations in some TCA cycle enzymes changed this view, indicating altered mitochondrial metabolism as an instrumental mechanism for cancer initiation. Similarly, the observation that TCA cycle-derived metabolites have multiple signaling roles in immune cells supports the idea of this pathway as a metabolic rheostat of immune responses. Critical Issues: This review summarizes the crucial role of the TCA cycle in pathophysiology describing the post-translational and epigenetic impact of oncometabolites accumulation in cancer and immune cells. Future Directions: Additional studies will be necessary to further explore the role of oncometabolites in paracrine signaling and to identify genuine metabolic and nutritional liabilities imposed by TCA cycle dysfunction in cancer, hardly to be escaped by resistance mechanisms.

journal_name

Antioxid Redox Signal

authors

Scagliola A,Mainini F,Cardaci S

doi

10.1089/ars.2019.7974

subject

Has Abstract

pub_date

2020-04-20 00:00:00

pages

834-852

issue

12

eissn

1523-0864

issn

1557-7716

journal_volume

32

pub_type

杂志文章
  • Thioredoxin 1-mediated post-translational modifications: reduction, transnitrosylation, denitrosylation, and related proteomics methodologies.

    abstract::Despite the significance of redox post-translational modifications (PTMs) in regulating diverse signal transduction pathways, the enzymatic systems that catalyze reversible and specific oxidative or reductive modifications have yet to be firmly established. Thioredoxin 1 (Trx1) is a conserved antioxidant protein that ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3831

    authors: Wu C,Parrott AM,Fu C,Liu T,Marino SM,Gladyshev VN,Jain MR,Baykal AT,Li Q,Oka S,Sadoshima J,Beuve A,Simmons WJ,Li H

    更新日期:2011-11-01 00:00:00

  • Selective Disruption of Respiratory Supercomplexes as a New Strategy to Suppress Her2high Breast Cancer.

    abstract:AIMS:Expression of the HER2 oncogene in breast cancer is associated with resistance to treatment, and Her2 may regulate bioenergetics. Therefore, we investigated whether disruption of the electron transport chain (ETC) is a viable strategy to eliminate Her2high disease. RESULTS:We demonstrate that Her2high cells and t...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2016.6677

    authors: Rohlenova K,Sachaphibulkij K,Stursa J,Bezawork-Geleta A,Blecha J,Endaya B,Werner L,Cerny J,Zobalova R,Goodwin J,Spacek T,Alizadeh Pesdar E,Yan B,Nguyen MN,Vondrusova M,Sobol M,Jezek P,Hozak P,Truksa J,Rohlena J,Do

    更新日期:2017-01-10 00:00:00

  • Selenoprotein K and protein palmitoylation.

    abstract:SIGNIFICANCE:Selenoprotein K (SelK) is an endoplasmic reticulum (ER) membrane protein, and its expression is sensitive to dietary selenium levels. A recently described role for SelK as a cofactor in catalyzing protein palmitoylation reactions provides an important link between low dietary selenium intake and suboptimal...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2015.6375

    authors: Fredericks GJ,Hoffmann PR

    更新日期:2015-10-01 00:00:00

  • Hypoxia-induced miR-210 modulates tissue response to acute peripheral ischemia.

    abstract:AIMS:Peripheral artery disease is caused by the restriction or occlusion of arteries supplying the leg. Better understanding of the molecular mechanisms underpinning tissue response to ischemia is urgently needed to improve therapeutic options. The aim of this study is to investigate hypoxia-induced miR-210 regulation ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2013.5206

    authors: Zaccagnini G,Maimone B,Di Stefano V,Fasanaro P,Greco S,Perfetti A,Capogrossi MC,Gaetano C,Martelli F

    更新日期:2014-09-10 00:00:00

  • Role of reactive oxygen species in neonatal pulmonary vascular disease.

    abstract:SIGNIFICANCE:Abnormal lung development in the perinatal period can result in severe neonatal complications, including persistent pulmonary hypertension (PH) of the newborn and bronchopulmonary dysplasia. Reactive oxygen species (ROS) play a substantive role in the development of PH associated with these diseases. ROS i...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5785

    authors: Wedgwood S,Steinhorn RH

    更新日期:2014-11-01 00:00:00

  • Glutathione S-Transferase P-Mediated Protein S-Glutathionylation of Resident Endoplasmic Reticulum Proteins Influences Sensitivity to Drug-Induced Unfolded Protein Response.

    abstract:AIMS:S-glutathionylation of cysteine residues, catalyzed by glutathione S-transferase Pi (GSTP), alters structure/function characteristics of certain targeted proteins. Our goal is to characterize how S-glutathionylation of proteins within the endoplasmic reticulum (ER) impact cell sensitivity to ER-stress inducing dru...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2015.6486

    authors: Ye ZW,Zhang J,Ancrum T,Manevich Y,Townsend DM,Tew KD

    更新日期:2017-02-20 00:00:00

  • Cell cycle regulators guide mitochondrial activity in radiation-induced adaptive response.

    abstract:SIGNIFICANCE:There are accruing concerns on potential genotoxic agents present in the environment including low-dose ionizing radiation (LDIR) that naturally exists on earth's surface and atmosphere and is frequently used in medical diagnosis and nuclear industry. Although its long-term health risk is being evaluated a...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5684

    authors: Alexandrou AT,Li JJ

    更新日期:2014-03-20 00:00:00

  • Metallothionein attenuates 3-morpholinosydnonimine (SIN-1)-induced oxidative stress in dopaminergic neurons.

    abstract::Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra zona compacta, and in other subcortical nuclei associated with a widespread occurrence of Lewy bodies. The causes of cell death in Parkinson's disease are still poorly understood, but a defect in mitochondrial ox...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/152308603322110832

    authors: Sharma SK,Ebadi M

    更新日期:2003-06-01 00:00:00

  • Signaling by the arc two-component system provides a link between the redox state of the quinone pool and gene expression.

    abstract::The Arc two-component system is a complex signal transduction system that plays a key role in regulating energy metabolism at the level of transcription in bacteria. This system comprises the ArcB protein, a tripartite membrane-associated sensor kinase, and the ArcA protein, a typical response regulator. Under anoxic ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2006.8.781

    authors: Malpica R,Sandoval GR,Rodríguez C,Franco B,Georgellis D

    更新日期:2006-05-01 00:00:00

  • Organic Isothiocyanates as Hydrogen Sulfide Donors.

    abstract:: Significance: Hydrogen sulfide (H2S), the "new entry" in the series of endogenous gasotransmitters, plays a fundamental role in regulating the biological functions of various organs and systems. Consequently, the lack of adequate levels of H2S may represent the etiopathoge...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2019.7888

    authors: Martelli A,Citi V,Testai L,Brogi S,Calderone V

    更新日期:2020-01-10 00:00:00

  • NQO1 Deficiency Leads Enhanced Autophagy in Cisplatin-Induced Acute Kidney Injury Through the AMPK/TSC2/mTOR Signaling Pathway.

    abstract:AIMS:Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study,...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2015.6386

    authors: Kim TW,Kim YJ,Kim HT,Park SR,Lee MY,Park YD,Lee CH,Jung JY

    更新日期:2016-05-20 00:00:00

  • Role of Nox family NADPH oxidases in host defense.

    abstract::The phagocytic NADPH oxidase is recognized as a critical component of innate immunity, responsible for generation of microbicidal reactive oxygen species (ROS). This enzyme is one representative of the Nox family of oxidases (Nox1-Nox5, Duox1, and Duox2) that exhibit diverse expression patterns and appear to serve a v...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2006.8.1549

    authors: Leto TL,Geiszt M

    更新日期:2006-09-01 00:00:00

  • PDE/cAMP/Epac/C/EBP-β Signaling Cascade Regulates Mitochondria Biogenesis of Tubular Epithelial Cells in Renal Fibrosis.

    abstract:AIMS:Cyclic adenosine 3'5'-monophosphate (cAMP) is a universal second messenger that plays an important role in intracellular signal transduction. cAMP is synthesized by adenylate cyclases from adenosine triphosphate and terminated by the phosphodiesterases (PDEs). In the present study, we investigated the role of the ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2017.7041

    authors: Ding H,Bai F,Cao H,Xu J,Fang L,Wu J,Yuan Q,Zhou Y,Sun Q,He W,Dai C,Zen K,Jiang L,Yang J

    更新日期:2018-09-01 00:00:00

  • Expanding insights on the involvement of endoplasmic reticulum stress in Parkinson's disease.

    abstract::Parkinson's disease (PD) is the second most common neurodegenerative disease characterized by selective loss of dopaminergic neurons and the presence of Lewy bodies. The pathogenesis of PD remains incompletely understood. Environmental factors, oxidative damage, misfolded protein aggregates, ubiquitin-proteasome syste...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2006.1524

    authors: Wang HQ,Takahashi R

    更新日期:2007-05-01 00:00:00

  • Genome-Scale Modeling of NADPH-Driven β-Lapachone Sensitization in Head and Neck Squamous Cell Carcinoma.

    abstract:AIMS:The purpose of this study was to investigate differential nicotinamide adenine dinucleotide phosphate, reduced (NADPH) production between radiation-sensitive and -resistant head and neck squamous cell carcinoma (HNSCC) cell lines and whether these differences are predictive of sensitivity to the chemotherapeutic β...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2017.7048

    authors: Lewis JE,Costantini F,Mims J,Chen X,Furdui CM,Boothman DA,Kemp ML

    更新日期:2018-10-01 00:00:00

  • Regulation of tumor necrosis factor-induced, mitochondria- and reactive oxygen species-dependent cell death by the electron flux through the electron transport chain complex I.

    abstract::Tumor necrosis factor (TNF) induces a caspase-independent but mitochondria-dependent cell death process in the mouse fibrosarcoma cell line L929. Mitochondria actively participate in this TNF-induced necrotic cell death by the generation of mitochondrial reactive oxygen species (ROS). The aim of this study was to iden...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.1999.1.3-285

    authors: Goossens V,Stangé G,Moens K,Pipeleers D,Grooten J

    更新日期:1999-10-01 00:00:00

  • The degradative inventory of the cell: proteomic insights.

    abstract:SIGNIFICANCE:Protein degradation has been identified as being deregulated in numerous human diseases. Hence, proteins involved in proteasomal as well as lysosomal degradation are regarded as interesting potential drug targets and are thoroughly investigated in clinical studies. RECENT ADVANCES:Technical advances in th...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2011.4393

    authors: Engelke R,Becker AC,Dengjel J

    更新日期:2012-09-01 00:00:00

  • Dysregulation of corticostriatal ascorbate release and glutamate uptake in transgenic models of Huntington's disease.

    abstract:SIGNIFICANCE:Dysregulation of cortical and striatal neuronal processing plays a critical role in Huntington's disease (HD), a dominantly inherited condition that includes a progressive deterioration of cognitive and motor control. Growing evidence indicates that ascorbate (AA), an antioxidant vitamin, is released into ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2013.5387

    authors: Rebec GV

    更新日期:2013-12-10 00:00:00

  • Hyperglycemia-induced reactive oxygen species and impaired endothelial progenitor cell function.

    abstract::Vascular complications in diabetes are a significant source of human morbidity and mortality, affecting multiple organ systems and persisting despite tight glucose control. Many of these complications can be linked to impairments in vasculogenesis, the process by which circulating and bone marrow-derived endothelial p...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2005.7.1476

    authors: Callaghan MJ,Ceradini DJ,Gurtner GC

    更新日期:2005-11-01 00:00:00

  • Mitochondrial plasticity in obesity and diabetes mellitus.

    abstract:SIGNIFICANCE:Insulin resistance and its related diseases, obesity and type 2 diabetes mellitus (T2DM), have been linked to changes in aerobic metabolism, pointing to a possible role of mitochondria in the development of insulin resistance. RECENT ADVANCES:Refined methodology of ex vivo high-resolution respirometry and...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2012.4910

    authors: Jelenik T,Roden M

    更新日期:2013-07-20 00:00:00

  • Free radicals in cross talk between autophagy and apoptosis.

    abstract:SIGNIFICANCE:Oxidative (reactive oxygen species [ROS]) and nitrosative (reactive nitrogen species [RNS]) stress affects many physiological processes, including survival and death. Although high levels of ROS/RNS mainly causes cell death, low levels of free radicals directly modulate the activities of transcriptional fa...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2013.5746

    authors: Kaminskyy VO,Zhivotovsky B

    更新日期:2014-07-01 00:00:00

  • Redox considerations in female reproductive function and assisted reproduction: from molecular mechanisms to health implications.

    abstract::Physiological levels of reactive oxygen species (ROS) play an important regulatory role through various signaling transduction pathways in folliculogenesis, oocyte maturation, endometrial cycle, luteolysis, implantation, embryogenesis, and pregnancy. Persistent and elevated generation of ROS leads to a disturbance of ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2007.1964

    authors: Agarwal A,Gupta S,Sekhon L,Shah R

    更新日期:2008-08-01 00:00:00

  • Reactive nitrogen and oxygen intermediates and bacterial defenses: unusual adaptations in Mycobacterium tuberculosis.

    abstract::The production of reactive oxygen and reactive nitrogen intermediates is an important host defense mechanism mediated in response to infection by bacterial pathogens. Not surprisingly, intracellular pathogens have evolved numerous defense strategies to protect themselves against the damaging effects of these agents. I...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/152308602753625924

    authors: Zahrt TC,Deretic V

    更新日期:2002-02-01 00:00:00

  • Alpha-Synuclein Oligomers Interact with Metal Ions to Induce Oxidative Stress and Neuronal Death in Parkinson's Disease.

    abstract:AIMS:Protein aggregation and oxidative stress are both key pathogenic processes in Parkinson's disease, although the mechanism by which misfolded proteins induce oxidative stress and neuronal death remains unknown. In this study, we describe how aggregation of alpha-synuclein (α-S) from its monomeric form to its solubl...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2015.6343

    authors: Deas E,Cremades N,Angelova PR,Ludtmann MH,Yao Z,Chen S,Horrocks MH,Banushi B,Little D,Devine MJ,Gissen P,Klenerman D,Dobson CM,Wood NW,Gandhi S,Abramov AY

    更新日期:2016-03-01 00:00:00

  • Pathobiology of junctional adhesion molecules.

    abstract::Junctional adhesion molecules are transmembrane proteins that belong to the immunoglobulin superfamily. In addition to their localization in close proximity to the tight junctions in endothelial and epithelial cells, junctional adhesion molecules are also expressed in circulating cells that do not form junctions, such...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3867

    authors: Bazzoni G

    更新日期:2011-09-01 00:00:00

  • H₂O₂-Activated Mitochondrial Phospholipase iPLA₂γ Prevents Lipotoxic Oxidative Stress in Synergy with UCP2, Amplifies Signaling via G-Protein-Coupled Receptor GPR40, and Regulates Insulin Secretion in Pancreatic β-Cells.

    abstract:AIMS:Pancreatic β-cell chronic lipotoxicity evolves from acute free fatty acid (FA)-mediated oxidative stress, unprotected by antioxidant mechanisms. Since mitochondrial uncoupling protein-2 (UCP2) plays antioxidant and insulin-regulating roles in pancreatic β-cells, we tested our hypothesis, that UCP2-mediated uncoupl...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2014.6195

    authors: Ježek J,Dlasková A,Zelenka J,Jabůrek M,Ježek P

    更新日期:2015-10-20 00:00:00

  • Anti-atherogenic effect of laminar shear stress via Nrf2 activation.

    abstract::Fluid shear stress plays a critical role in the regulation of vascular biology and its pathology, such as atherosclerosis, via modulation of redox balance. Both pro-atherogenic (either oscillatory or turbulent, nonunidirectional) shear stress and anti-atherogenic (either steady or pulsatile, unidirectional laminar) sh...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3433

    authors: Takabe W,Warabi E,Noguchi N

    更新日期:2011-09-01 00:00:00

  • Augmentation of S-Nitrosoglutathione Controls Cigarette Smoke-Induced Inflammatory-Oxidative Stress and Chronic Obstructive Pulmonary Disease-Emphysema Pathogenesis by Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function.

    abstract:AIMS:Cigarette smoke (CS)-mediated acquired cystic fibrosis transmembrane conductance regulator (CFTR)-dysfunction, autophagy-impairment, and resulting inflammatory-oxidative/nitrosative stress leads to chronic obstructive pulmonary disease (COPD)-emphysema pathogenesis. Moreover, nitric oxide (NO) signaling regulates ...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2016.6895

    authors: Bodas M,Silverberg D,Walworth K,Brucia K,Vij N

    更新日期:2017-09-01 00:00:00

  • Disulfide reduction in the endocytic pathway: immunological functions of gamma-interferon-inducible lysosomal thiol reductase.

    abstract::Gamma-interferon-inducible lysosomal thiol reductase (GILT) is constitutively expressed in most antigen presenting cells and is interferon γ inducible in other cell types via signal transducer and activator of transcription 1. Normally, N- and C-terminal propeptides are cleaved in the early endosome, and the mature pr...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章,评审

    doi:10.1089/ars.2010.3684

    authors: Hastings KT,Cresswell P

    更新日期:2011-08-01 00:00:00

  • Contribution of thioredoxin reductase to T-cell mitogenesis and NF-kappaB DNA-binding promoted by selenite.

    abstract::Although the essential role of selenium for cellular immune responses is obvious, delineation of the functions is lacking because selenium can either promote or inhibit cell growth, cytokine production, and activation of transcription factor nuclear factor-kappaB (NF-kappaB). Studies with human thioredoxin-1 (Trx-1)-t...

    journal_title:Antioxidants & redox signaling

    pub_type: 杂志文章

    doi:10.1089/ars.2007.9.115

    authors: Ueno H,Kajihara H,Nakamura H,Yodoi J,Nakamuro K

    更新日期:2007-01-01 00:00:00