Online citations, reference lists, and bibliographies.
← Back to Search

Role For Mitochondrial Oxidants As Regulators Of Cellular Metabolism

S. Nemoto, K. Takeda, Zu-Xi Yu, V. Ferrans, T. Finkel
Published 2000 · Biology, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy Visualize in Litmaps
Share
Reduce the time it takes to create your bibliography by a factor of 10 by using the world’s favourite reference manager
Time to take this seriously.
Get Citationsy
ABSTRACT Leakage of mitochondrial oxidants contributes to a variety of harmful conditions ranging from neurodegenerative diseases to cellular senescence. We describe here, however, a physiological and heretofore unrecognized role for mitochondrial oxidant release. Mitochondrial metabolism of pyruvate is demonstrated to activate the c-Jun N-terminal kinase (JNK). This metabolite-induced rise in cytosolic JNK1 activity is shown to be triggered by increased release of mitochondrial H2O2. We further demonstrate that in turn, the redox-dependent activation of JNK1 feeds back and inhibits the activity of the metabolic enzymes glycogen synthase kinase 3β and glycogen synthase. As such, these results demonstrate a novel metabolic regulatory pathway activated by mitochondrial oxidants. In addition, they suggest that although chronic oxidant production may have deleterious effects, mitochondrial oxidants can also function acutely as signaling molecules to provide communication between the mitochondria and the cytosol.
This paper references
10.1042/BJ1340707
The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen.
A. Boveris (1973)
10.1111/J.1432-1033.1978.TB12051.X
Do mitochondria produce oxygen radicals in vivo?
H. Nohl (1978)
10.1016/0014-5793(79)80515-3
Glycogen synthase: A new activity ratio assay expressing a high sensitivity to the phosphorylation state
J. Guinovart (1979)
10.1161/01.RES.74.6.1141
Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells.
K. Griendling (1994)
10.1126/science.270.5234.296
Requirement for Generation of H2O2 for Platelet-Derived Growth Factor Signal Transduction
M. Sundaresan (1995)
[Pathophysiology of insulin resistance].
H. Häring (1995)
10.1128/MCB.15.8.4353
RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence: growth factor-stimulated kinase function and nuclear translocation
Y. Zhao (1995)
10.1074/jbc.271.48.30765
jun N-terminal Kinase Mediates Activation of Skeletal Muscle Glycogen Synthase by Insulin in Vivo*
C. Moxham (1996)
10.1126/SCIENCE.273.5271.59
Oxidative Stress, Caloric Restriction, and Aging
R. S. Sohal (1996)
10.1042/BJ3180379
Regulation of reactive-oxygen-species generation in fibroblasts by Rac1.
M. Sundaresan (1996)
10.1128/MCB.16.12.7115
rac1 regulates a cytokine-stimulated, redox-dependent pathway necessary for NF-kappaB activation
D. Sulciner (1996)
10.1096/fasebj.11.2.9039953
An essential role for free radicals and derived species in signal transduction
H. Lander (1997)
10.1006/EXCR.1997.3779
Stimulation of oxygen consumption promotes mitochondrial calcium accumulation, a process associated with, and causally linked to, enhanced formation of tert-butylhydroperoxide-induced DNA single-strand breaks.
A. Guidarelli (1997)
10.1126/SCIENCE.275.5306.1649
Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts
K. Irani (1997)
10.1006/BBRC.1997.6835
Effect of oncogene transformation of rat embryo cells on cellular oxygen consumption and glycolysis.
J. Biaglow (1997)
Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation
Y. S. Bae (1997)
10.1074/jbc.273.29.17991
A Rac1 Effector Site Controlling Mitogenesis through Superoxide Production*
T. Joneson (1998)
10.1126/SCIENCE.280.5365.898
Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change.
F. Kheradmand (1998)
10.1172/JCI2552
A requirement for the rac1 GTPase in the signal transduction pathway leading to cardiac myocyte hypertrophy.
J. Pracyk (1998)
10.1074/jbc.273.45.29986
Involvement of Tyrosine Phosphorylation and Protein Kinase C in the Activation of Phospholipase D by H2O2 in Swiss 3T3 Fibroblasts*
D. Min (1998)
10.1152/PHYSREV.1998.78.2.547
The free radical theory of aging matures.
K. Beckman (1998)
10.1016/S0092-8674(00)81405-1
Reactive Oxygen Intermediates Mediate a Systemic Signal Network in the Establishment of Plant Immunity
M. .. Alvarez (1998)
10.1016/S0955-0674(98)80147-6
Oxygen radicals and signaling.
T. Finkel (1998)
10.1038/448
Radicals r'aging
D. Wallace (1998)
10.1091/MBC.9.3.561
The Ras/Rac1/Cdc42/SEK/JNK/c-Jun cascade is a key pathway by which agonists stimulate DNA synthesis in primary cultures of rat hepatocytes.
K. L. Auer (1998)
10.1016/S0165-6147(98)01230-9
Glutamate transporters are oxidant-vulnerable: a molecular link between oxidative and excitotoxic neurodegeneration?
D. Trotti (1998)
10.1074/JBC.273.25.15366
Reversible Inactivation of Protein-tyrosine Phosphatase 1B in A431 Cells Stimulated with Epidermal Growth Factor*
Seung-Rock Lee (1998)
10.1006/ABBI.1997.0489
Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria.
L. Kwong (1998)
Superoxide in apoptosis: mitochondrial generation triggered by cytochrome c loss
J. Cai (1998)
10.1074/jbc.274.48.33881
Glutathione Levels Discriminate between Oxidative Stress and Transforming Growth Factor-β Signaling in Activated Rat Hepatic Stellate Cells*
P. de Bleser (1999)
10.1038/emm.1999.9
Redox signaling: hydrogen peroxide as intracellular messenger
S. Rhee (1999)
10.1074/jbc.274.12.7936
Ras Proteins Induce Senescence by Altering the Intracellular Levels of Reactive Oxygen Species*
Andrew C. Lee (1999)
10.1038/43459
Cell transformation by the superoxide-generating oxidase Mox1
Y. Suh (1999)
10.1074/jbc.274.46.32596
Hydrogen Peroxide Activates p70S6k Signaling Pathway*
G. Bae (1999)
10.1093/emboj/18.5.1321
Regulation of JNK signaling by GSTp
V. Adler (1999)
10.1074/jbc.274.32.22699
Reactive Oxygen Species Mediate the Activation of Akt/Protein Kinase B by Angiotensin II in Vascular Smooth Muscle Cells*
M. Ushio-Fukai (1999)
10.1210/ENDO.140.5.6699
RO 31-8220 activates c-Jun N-terminal kinase and glycogen synthase in rat adipocytes and L6 myotubes. Comparison to actions of insulin.
M. Standaert (1999)
10.1111/j.1525-1373.2000.22319.x
Pyruvate: metabolic protector of cardiac performance.
R. Mallet (2000)
10.1126/SCIENCE.287.5450.138
A mammalian H+ channel generated through alternative splicing of the NADPH oxidase homolog NOH-1.
B. Bánfi (2000)
10.1080/026404100365117
Changes in blood lactate and pyruvate concentrations and the lactate-to-pyruvate ratio during the lactate minimum speed test
H. Carter (2000)
10.1038/35008121
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
T. Nishikawa (2000)



This paper is referenced by
10.1038/s41408-021-00484-6
SIRT3 overexpression and epigenetic silencing of catalase regulate ROS accumulation in CLL cells activating AXL signaling axis
G. Maiti (2021)
10.1007/s10753-021-01509-9
ATN-161 Ameliorates Ischemia/Reperfusion-induced Oxidative Stress, Fibro-inflammation, Mitochondrial damage, and Apoptosis-mediated Tight Junction Disruption in bEnd.3 Cells
N. Amruta (2021)
10.1007/s10565-021-09605-0
Pyruvate kinase M2 in chronic inflammations: a potpourri of crucial protein-protein interactions.
Sagarkumar Patel (2021)
10.1016/bs.vh.2020.12.017
Relaxin abrogates genomic remodeling of the aged heart.
Guillermo Romero (2021)
10.3390/molecules26164913
The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant
C. J. Jong (2021)
10.15252/embj.2020106106
Dual targeting of brain region‐specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1
W. Lee (2021)
10.1016/j.molmet.2021.101234
The brain as an insulin-sensitive metabolic organ.
J. Milstein (2021)
10.1016/j.redox.2021.101947
NOX4 promotes ferroptosis of astrocytes by oxidative stress-induced lipid peroxidation via the impairment of mitochondrial metabolism in Alzheimer's diseases
Min Woo Park (2021)
10.1016/j.bbrep.2021.100998
Effect of magnesium sulfate in oxidized lipid bilayers properties by using molecular dynamics
Miguel Fernández (2021)
10.1155/2020/2468031
Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats
Mengqi Gong (2020)
10.1101/2020.09.21.305847
High-dose pyruvate treatment alters skeletal muscle differentiation and expression of inflammation-related genes
K. Hasegawa (2020)
10.3390/f11020189
Individual Cryptomeria fortunei Hooibrenk Clones Show Varying Degrees of Chilling Stress Resistance
Yingting Zhang (2020)
10.3390/medicina56110626
Mini-Review on Lipofuscin and Aging: Focusing on The Molecular Interface, The Biological Recycling Mechanism, Oxidative Stress, and The Gut-Brain Axis Functionality
O. Ilie (2020)
10.3389/fcell.2020.608026
Mitochondrial Dysfunction in Astrocytes: A Role in Parkinson’s Disease?
C. Bantle (2020)
10.3390/genes11010086
Mitochondrial DNA: A Key Regulator of Anti-Microbial Innate Immunity
S. Kausar (2020)
10.1016/j.freeradbiomed.2020.12.019
ROS signaling capacity of cytochrome bc1: opposing effects of adaptive and pathogenic mitochondrial mutations.
Jakub Pagacz (2020)
10.5772/intechopen.91769
Predictive and Prognosis Factors of Clinical Utility in Mesothelioma
Rodríguez-Cid Jeronimo Rafael (2020)
10.3390/cells9030702
Tissue-Specific Metabolic Regulation of FOXO-Binding Protein: FOXO Does Not Act Alone
N. Kodani (2020)
10.1007/s00424-020-02458-2
Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts.
Yu Na Wu (2020)
10.1038/s41540-020-00150-w
ROS networks: designs, aging, Parkinson’s disease and precision therapies
Alexey N Kolodkin (2020)
10.3390/ijms20215266
The Crosstalk of miRNA and Oxidative Stress in the Liver: From Physiology to Pathology and Clinical Implications
E. Klieser (2019)
10.1177/1933719118766264
Changes in Metabolism, Mitochondrial Function, and Oxidative Stress Between Female Rats Under Nonreproductive and 3 Reproductive Conditions
H. Hyatt (2019)
10.1111/apha.13430
Altered mitochondrial metabolism in the insulin‐resistant heart
M. Makrecka-Kuka (2019)
10.1556/650.2019.31519
A karbonilstressz szerepe a diabetes szövődményeinek kialakulásában
Kinga Makk-Merczel (2019)
10.1155/2019/5153268
Reactive Oxygen Species and Nrf2: Functional and Transcriptional Regulators of Hematopoiesis
Linping Hu (2019)
10.1007/978-981-13-8946-7_9
Heat Shock Proteins and Their Associated Oxidative Stress-Induced Heart Disease
Sangeeta Mitra (2019)
10.1007/978-981-13-8946-7_13
Oxidative Stress as a Critical Determinant of Adult Cardiac Progenitor Cell-Fate Decisions
D. Herrero (2019)
10.1016/J.NUT.2019.03.022
Refeeding abolishes beneficial effects of severe calorie restriction from birth on adipose tissue and glucose homeostasis of adult rats.
D. S. Melo (2019)
10.4187/respcare.05618
Low-Flow Domiciliary Oxygen as a Mechanism of Ongoing Oxidative Stress
Jill M. Stulce (2019)
10.7717/peerj.6766
Leaf anatomy and ultrastructure in senescing ancient tree, Platycladus orientalis L. (Cupressaceae)
Q. Zhou (2019)
10.1002/cphy.c180043
Mesenchymal Regulation of the Microvascular Niche in Chronic Lung Diseases.
S. Majka (2019)
10.15381/RIVEP.V30I1.15703
Parámetros metabólicos, antioxidantes y competencia para el desarrollo embrionario de ovocitos bovinos madurados in vitro con L-Carnitina
Natalia Jaramillo Bolívar (2019)
See more
Semantic Scholar Logo Some data provided by SemanticScholar