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Abstract
Apoptosis or programmed cell death represents a physiologically conserved mechanism of cell death that is pivotal in normal development and tissue homeostasis in all organisms. As a key modulator of cell functions, the most abundant non-protein thiol, glutathione (GSH), has important roles in cellular defense against oxidant aggression, redox regulation of proteins thiols and maintaining redox homeostasis that is critical for proper function of cellular processes, including apoptosis. Thus, a shift in the cellular GSH-to-GSSG redox balance in favour of the oxidized species, GSSG, constitutes an important signal that could decide the fate of a cell. The current review will focus on three main areas: (1) general description of cellular apoptotic pathways, (2) cellular compartmentation of GSH and the contribution of mitochondrial GSH and redox proteins to apoptotic signalling and (3) role of redox mechanisms in the initiation and execution phases of apoptosis.
| Abbreviations | ||
| γ-GGT | = | γ-glutamyltransferase |
| ADP | = | adenosine diphosphate |
| AIF | = | apoptosis inducing factor |
| Apaf-1 | = | apoptotic protease activation factor-1 |
| APE | = | apurinic/apyrimidinic endonuclease |
| ASK-1 | = | -2, apoptosis signal-regulating kinase 1, -2 |
| ATP | = | adenosine triphosphate |
| Bax | = | pro-apoptotic protein Bax |
| Bcl-2 | = | anti-apoptotic protein |
| BER | = | base excision repair |
| Bid | = | BH3-only pro-apoptotic protein Bid |
| BIR | = | Baculovirus IAP repeat |
| BSO | = | buthionine sulphoximine |
| CARD | = | caspase activation and recruiting domain |
| caspase-8,-9,-3 | = | active form of caspase-8,-9,-3 |
| CJ | = | cristae junction |
| CL | = | cardiolipin |
| CL-OOH | = | peroxidized cardiolipin |
| cypD | = | cyclophylin D |
| Cys | = | cysteine |
| cyt c | = | cytochrome c |
| DCVC | = | S-(1,2-dichlorevinyl)-L-cysteine |
| DED | = | death effector domain |
| DIC | = | dicarboxylate carrier |
| DISC | = | death-inducing signalling complex |
| DP | = | dipeptidase |
| ER | = | endoplasmic reticulum |
| FADD | = | Fas-associated death domain |
| FasL | = | Fas ligand |
| G6PD | = | glucose-6-phosphate dehydrogenase |
| GAPDH | = | glyceraldehyde-3-phospate dehydrogenase |
| GCL | = | glutamate-cysteine ligase |
| Glu | = | glutamic acid |
| Gly | = | glycine |
| GPx | = | GSH peroxidase |
| GR | = | GSH reductase |
| GS | = | glutathione synthase |
| GSH | = | glutathione |
| GSSG | = | glutathione disulphide |
| H2O2 | = | hydrogen peroxide |
| HDM2 | = | human double minute 2 protein |
| IAA | = | iodoacetic acid |
| JNK | = | c-Jun N-terminal kinase |
| MPT | = | mitochondrial permeability transition |
| mtDNA | = | mitochondrial DNA |
| mtGSH/GSSG | = | mitochondrial GSH/GSSG |
| NAC | = | N-acetylcysteine |
| NER | = | nucleotide excision repair |
| NO• | = | nitric oxide |
| OGC | = | oxo-glutarate carrier |
| OGG1 | = | 8-oxodG glycosylase |
| OPA1 | = | optic atrophya 1 protein |
| PTP | = | permeability transition pore |
| ROS | = | reactive oxygen species |
| RNO | = | reactive nitrogen species |
| Smac/Diablo | = | second mitochondria-derived activator of caspases/direct IAP binding protein with low pI |
| tBH | = | tert-butyl hydroperoxide |
| tBid | = | truncated form of Bid |
| TCDD | = | 2,3,7,8-tetrachloredibenzo-p-dioxin |
| TRAF2/6 | = | TNFα receptor-associated factor 2/6 |
| Trx1 | = | thioredoxin 1, reduced form |
| Trx2 | = | thioredoxin 2, reduced form |
| TRX-S-S | = | thioredoxin, oxidized form |
| UPR | = | unfolding protein response |
| VDAC | = | voltage-dependent anion channel |
| Abbreviations | ||
| γ-GGT | = | γ-glutamyltransferase |
| ADP | = | adenosine diphosphate |
| AIF | = | apoptosis inducing factor |
| Apaf-1 | = | apoptotic protease activation factor-1 |
| APE | = | apurinic/apyrimidinic endonuclease |
| ASK-1 | = | -2, apoptosis signal-regulating kinase 1, -2 |
| ATP | = | adenosine triphosphate |
| Bax | = | pro-apoptotic protein Bax |
| Bcl-2 | = | anti-apoptotic protein |
| BER | = | base excision repair |
| Bid | = | BH3-only pro-apoptotic protein Bid |
| BIR | = | Baculovirus IAP repeat |
| BSO | = | buthionine sulphoximine |
| CARD | = | caspase activation and recruiting domain |
| caspase-8,-9,-3 | = | active form of caspase-8,-9,-3 |
| CJ | = | cristae junction |
| CL | = | cardiolipin |
| CL-OOH | = | peroxidized cardiolipin |
| cypD | = | cyclophylin D |
| Cys | = | cysteine |
| cyt c | = | cytochrome c |
| DCVC | = | S-(1,2-dichlorevinyl)-L-cysteine |
| DED | = | death effector domain |
| DIC | = | dicarboxylate carrier |
| DISC | = | death-inducing signalling complex |
| DP | = | dipeptidase |
| ER | = | endoplasmic reticulum |
| FADD | = | Fas-associated death domain |
| FasL | = | Fas ligand |
| G6PD | = | glucose-6-phosphate dehydrogenase |
| GAPDH | = | glyceraldehyde-3-phospate dehydrogenase |
| GCL | = | glutamate-cysteine ligase |
| Glu | = | glutamic acid |
| Gly | = | glycine |
| GPx | = | GSH peroxidase |
| GR | = | GSH reductase |
| GS | = | glutathione synthase |
| GSH | = | glutathione |
| GSSG | = | glutathione disulphide |
| H2O2 | = | hydrogen peroxide |
| HDM2 | = | human double minute 2 protein |
| IAA | = | iodoacetic acid |
| JNK | = | c-Jun N-terminal kinase |
| MPT | = | mitochondrial permeability transition |
| mtDNA | = | mitochondrial DNA |
| mtGSH/GSSG | = | mitochondrial GSH/GSSG |
| NAC | = | N-acetylcysteine |
| NER | = | nucleotide excision repair |
| NO• | = | nitric oxide |
| OGC | = | oxo-glutarate carrier |
| OGG1 | = | 8-oxodG glycosylase |
| OPA1 | = | optic atrophya 1 protein |
| PTP | = | permeability transition pore |
| ROS | = | reactive oxygen species |
| RNO | = | reactive nitrogen species |
| Smac/Diablo | = | second mitochondria-derived activator of caspases/direct IAP binding protein with low pI |
| tBH | = | tert-butyl hydroperoxide |
| tBid | = | truncated form of Bid |
| TCDD | = | 2,3,7,8-tetrachloredibenzo-p-dioxin |
| TRAF2/6 | = | TNFα receptor-associated factor 2/6 |
| Trx1 | = | thioredoxin 1, reduced form |
| Trx2 | = | thioredoxin 2, reduced form |
| TRX-S-S | = | thioredoxin, oxidized form |
| UPR | = | unfolding protein response |
| VDAC | = | voltage-dependent anion channel |