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

Does The Redox Status Of Cytochrome C Act As A Fail-safe Mechanism In The Regulation Of Programmed Cell Death?

J. Hancock, R. Desikan, S. Neill
Published 2001 · Chemistry, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
It has now become recognized that one of the key events in the induction of apoptosis, or programmed cell death, in both plants and animals is the release of cytochrome c from mitochondria. It is also known that oxidative stress imposed on cells can have a profound effect on the onset or progression of apoptosis. Here, we discuss how the redox status of cytochrome c, and thus its structure, can be altered by the presence of reactive oxygen species (ROS) and reduced glutathione (GSH). We suggest that cytochrome c will only induce programmed cell death if present in the cytoplasm in the oxidized state, and that the presence of high levels of cytoplasmic GSH maintain cytochrome c in an inactive (reduced) state, thus behaving as a fail-safe mechanism if cytochrome c is released by mitochondria when programmed cell death is not the required outcome. If the redox status of the cell is disturbed however, perhaps in the presence of hydrogen peroxide, GSH concentrations will drop, the cellular E(h) will rise, and cytochrome c will tend towards the oxidized state, allowing programmed cell death to proceed. Therefore, we propose that the redox state of cytoplasmic cytochrome c may be a key regulator of programmed cell death.
This paper references
10.1023/A:1005427919188
Mitochondrial Oxygen Radical Generation and Leak: Sites of Production in States 4 and 3, Organ Specificity, and Relation to Aging and Longevity
G. Barja (1999)
10.1016/S0092-8674(00)80434-1
Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li (1997)
10.1126/SCIENCE.7618081
Inhibitor-enhanced electron transfer: copper cytochrome c as a redox-inert probe of ternary complexes.
J. S. Zhou (1995)
10.1016/S0968-0004(96)40002-0
Diverse molecular provocation of programmed cell death.
I. Wertz (1996)
10.1080/07391102.1994.10508758
Comparison of protein structures in solution using local conformations derived from NMR data: application to cytochrome c.
L. Kar (1994)
10.1084/JEM.184.3.1155
Mitochondrial permeability transition is a central coordinating event of apoptosis
P. Marchetti (1996)
10.1042/BST0290345
Role of reactive oxygen species in cell signalling pathways.
J. Hancock (2001)
10.1016/S0968-0004(00)01658-3
Novel homologs of gp91phox.
J. Lambeth (2000)
10.1016/S0006-3495(96)79497-3
Molecular dynamics simulations of a protein on hydrophobic and hydrophilic surfaces.
D. Tobias (1996)
10.1016/S0006-2952(98)00227-5
Reactive oxygen intermediates as mediators of programmed cell death in plants and animals.
T. Jabs (1999)
10.1038/sj.cdd.4400722
Bcl-2 prevents mitochondrial permeability transition and cytochrome c release via maintenance of reduced pyridine nucleotides
A. Kowaltowski (2000)
10.1016/S0092-8674(00)80501-2
Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
H. Zou (1997)
10.1016/S0005-2728(98)00109-1
Mitochondrial control of apoptosis: the role of cytochrome c.
J. Cai (1998)
10.1038/10034
Hidden powers of the mitochondria
E. Alnemri (1999)
10.1126/SCIENCE.275.5303.1129
Prevention of Apoptosis by Bcl-2: Release of Cytochrome c from Mitochondria Blocked
J. Yang (1997)
10.1016/S0891-5849(99)00145-8
Glutathione redox potential in response to differentiation and enzyme inducers.
W. Kirlin (1999)
10.1016/0003-9861(85)90293-0
Ubisemiquinone is the electron donor for superoxide formation by complex III of heart mitochondria.
J. Turrens (1985)
10.1006/ABBI.1997.0324
Redox-dependent conformational changes are common structural features of cytochrome c from various species.
J. F. Calvert (1997)
10.1038/35041687
Oxidants, oxidative stress and the biology of ageing
T. Finkel (2000)
10.1016/0014-5793(83)80200-2
Effect of electron transfer inhibitors on superoxide generation in the cytochrome bc 1 site of the mitochondrial respiratory chain
M. Ksenzenko (1983)
10.1146/ANNUREV.ARPLANT.49.1.249
ASCORBATE AND GLUTATHIONE: Keeping Active Oxygen Under Control.
G. Noctor (1998)
10.1083/jcb.144.2.281
Ordering the Cytochrome c–initiated Caspase Cascade: Hierarchical Activation of Caspases-2, -3, -6, -7, -8, and -10 in a Caspase-9–dependent Manner
E. Slee (1999)
10.1021/BI00017A006
Structure of zinc-substituted cytochrome c: nuclear magnetic resonance and optical spectroscopic studies.
H. Anni (1995)
10.1042/BJ3300115
Harpin and hydrogen peroxide both initiate programmed cell death but have differential effects on defence gene expression in Arabidopsis suspension cultures.
R. Desikan (1998)
10.1093/emboj/16.15.4639
Cytochrome c activation of CPP32‐like proteolysis plays a critical role in a Xenopus cell‐free apoptosis system
R. Kluck (1997)
10.1042/BJ3410233
The mitochondrial permeability transition pore and its role in cell death.
M. Crompton (1999)
10.1111/j.1532-5415.1972.tb00787.x
The Biologic Clock: The Mitochondria?
D. Harman (1972)
10.1016/S0076-6879(94)33025-5
Assays of plasma membrane NADPH oxidase.
O. Jones (1994)
10.1016/S1567-7249(01)00008-3
A proposed mechanism for the lowering of mitochondrial electron leak by caloric restriction.
A. Grey (2001)
10.1182/BLOOD.V93.5.1464.405A32_1464_1476
NADPH Oxidase: An Update
B. Babior (1999)
10.1093/GERONJ/11.3.298
Aging: a theory based on free radical and radiation chemistry.
D. Harman (1956)
10.1038/sj.cdd.4400544
Analysis of redox regulation of cytochrome c-induced apoptosis in a cell-free system
Z. Pan (1999)
10.1016/S0891-5849(00)00336-1
Detection of superoxide anion released extracellularly by endothelial cells using cytochrome c reduction, ESR, fluorescence and lucigenin-enhanced chemiluminescence techniques.
M. Barbacanne (2000)
10.1016/0165-2478(95)00004-O
Effects of N-acetyl-L-cysteine on T-cell apoptosis are not mediated by increased cellular glutathione.
D. Jones (1995)
10.1016/S0092-8674(00)80849-1
Cytochrome c Deficiency Causes Embryonic Lethality and Attenuates Stress-Induced Apoptosis
K. Li (2000)
10.1016/S0167-5699(97)80014-X
[Mitochondrial control of apoptosis].
G. Kroemer (2001)
10.1021/BI00091A047
Resonance Raman study of the interactions between cytochrome c variants and cytochrome c oxidase.
P. Hildebrandt (1993)
10.3109/10715769509065273
The origin of the oxidative burst in plants.
G. Bolwell (1995)
10.1074/jbc.275.21.16127
Determinants of Cytochrome c Pro-apoptotic Activity
R. Kluck (2000)
10.1042/BJ3290095
Importance of the redox state of cytochrome c during caspase activation in cytosolic extracts.
M. Hampton (1998)
10.1006/CIMM.1997.1113
Apoptosis of myelin-reactive T cells induced by reactive oxygen and nitrogen intermediates in vitro.
U. Zettl (1997)
10.1042/BJ2530287
The potential diagram for oxygen at pH 7.
P. M. Wood (1988)
10.1126/SCIENCE.281.5381.1309
Mitochondria and apoptosis.
D. Green (1998)
10.1007/978-3-0348-8482-2_4
The NADPH oxidase of neutrophils and other cells
O. T. Jones (2000)
10.1016/S0014-5793(98)00061-1
Cytochrome c in the apoptotic and antioxidant cascades
V. Skulachev (1998)
10.1080/10715769900300271
Reactive oxygen intermediates regulate cellular response to apoptotic stimuli: an hypothesis.
M. Clément (1999)
10.1084/JEM.182.2.367
Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death
N. Zamzami (1995)
10.1126/SCIENCE.275.5303.1132
The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis
R. Kluck (1997)



This paper is referenced by
10.1167/IOVS.03-1081
Downregulation of ATP synthase subunit-6, cytochrome c oxidase-III, and NADH dehydrogenase-3 by bright cyclic light in the rat retina.
H. Huang (2004)
The molecular intersection between axon-specific pruning and neuronal apoptosis
Corey L. Cusack (2014)
10.1023/A:1024925612233
Radiation protection of HepG2 cells by Podophyllum hexandrum Royale
D. Gupta (2004)
10.1042/BJ20050580
Suppression of the pro-apoptotic function of cytochrome c by singlet oxygen via a haem redox state-independent mechanism.
D. Suto (2005)
10.1038/cr.2009.60
An agonistic monoclonal antibody against DR5 induces ROS production, sustained JNK activation and Endo G release in Jurkat leukemia cells
Caifeng Chen (2009)
10.1007/978-1-4939-9463-2_15
Equations to Support Redox Experimentation.
J. Hancock (2019)
10.1079/BJN20041259
In vitro folate supplementation alleviates oxidative stress, mitochondria-associated death signalling and apoptosis induced by 7-ketocholesterol.
R. S. Huang (2004)
10.1016/B978-0-12-405885-9.00004-8
Diabetic Retinopathy and Oxidative Stress
J. J. Garcia-Medina (2014)
10.4172/2155-6156.1000111
Antioxidants in the Prevention and Treatment of Diabetic Retinopathy - A Review
S. Silva (2010)
10.1089/ars.2007.1957
Redox regulation of cell survival.
D. Trachootham (2008)
10.1111/febs.14970
Apoptotic cell death regulation in neurons
Emilie Hollville (2019)
AMALAKI RASAYAN AS ANTIOXIDANT IN DIABETIC RETINOPATHY – REVIEW
Dr. Tanvir Patel (2019)
10.1007/s00249-003-0306-y
Conformational equilibria and dynamics of cytochrome c induced by binding of sodium dodecyl sulfate monomers and micelles
S. Oellerich (2003)
10.1016/J.JTBI.2003.08.003
New equations for redox and nano-signal transduction.
J. Hancock (2004)
Conceptos actuales del metabolismo del glutatión Utilización de los isótopos estables para la evaluación de su homeostasis
M. M. Sarrasague (2006)
10.1046/J.1365-313X.2003.01655.X
Changes in hydrogen peroxide homeostasis trigger an active cell death process in tobacco.
J. Dat (2003)
10.18240/ijo.2017.07.05
Pigment epithelium-derived factor protects retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction.
Shu-wei Tian (2017)
10.1074/jbc.M700322200
Mitochondrial Regulation of Caspase Activation by Cytochrome Oxidase and Tetramethylphenylenediamine via Cytosolic Cytochrome c Redox State*
V. Borutaite (2007)
10.1046/J.1432-1033.2003.03765.X
Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis.
M. Zhao (2003)
10.1016/J.TAAP.2003.10.008
Activation of plasma membrane reduced glutathione transport in death receptor apoptosis of HepG2 cells.
C. Hammond (2004)
10.1016/S0891-5849(03)00060-1
Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases.
A. Shukla (2003)
10.1074/JBC.M201002200
Cytochrome c Sorption-Desorption Effects on the External NADH Oxidation by Mitochondria
V. Lemeshko (2002)
Induction of redox imbalance and apoptosis in multiple myeloma cells by the novel triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid.
T. Ikeda (2004)
10.1016/S0981-9428(03)00135-9
The antioxidant systems vis-à-vis reactive oxygen species during plant–pathogen interaction
L. Gara (2003)
10.5487/TR.2014.30.4.221
A Panoramic Overview of Mitochondria and Mitochondrial Redox Biology
Aekyong Kim (2014)
10.1016/j.foodres.2018.05.049
Effect of mitochondrial cytochrome c release and its redox state on the mitochondrial-dependent apoptotic cascade reaction and tenderization of yak meat during postmortem aging.
L. Wang (2018)
10.1016/j.bmc.2013.09.025
Synthesis, antiproliferative and mitochondrial impairment activities of bis-alkyl-amino transplatinum complexes.
L. Dalla Via (2013)
10.1007/s00018-003-3272-8
Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells
J. H. Jeng (2003)
10.1007/s00418-004-0674-0
Mitochondrial transmembrane potential is diminished in phorbol myristate acetate-stimulated peritoneal resident macrophages isolated from wild-type mice, but not in those from gp91-phox-deficient mice
T. Kobayashi (2004)
10.1111/j.0906-6705.2005.00238.x
Ultraviolet A and B affect human melanocytes and keratinocytes differently. A study of oxidative alterations and apoptosis
P. Larsson (2005)
10.1007/s00726-009-0293-0
Mitochondrial damage, cytotoxicity and apoptosis in iron-potentiated alcoholic liver fibrosis: amelioration by taurine
S. Lakshmi Devi (2009)
10.1007/978-0-387-30411-3_19
5.3 Mitochondrial Production of Oxidants and Their Role in the Regulation of Cellular Processes
P. Brookes (2007)
See more
Semantic Scholar Logo Some data provided by SemanticScholar