New evidence suggests that physiological and damaging agents activate two different pathways of apoptotic signalling, which are mediated by protein-protein interactions and mitochondrial alterations respectively. The two pathways converge at the activation of caspase 3, the key effector of the execution phase of apoptosis, thus giving similar final results. The knowledge that different biochemical routes exist allows us to re-evaluate previous apparently contradictory results concerning the events occurring during apoptosis, and their respective roles. In particular, this applies to the role of oxidative stress and redox imbalance in the signal transduction events of apoptosis. It now appears that oxidative alterations are absent, or at least unnecessary, for the development of the physiological pathway. Instead, clear indications are emerging showing that redox imbalance is required for the damage-induced mitochondrial pathway. This is suggested by the finding that the depletion of glutathione, a common event in damage-induced apoptosis, is necessary and sufficient to induce cytochrome c release, the key event of this pathway. A model is proposed with GSH efflux as the backbone of the damage-induced apoptotic pathway.

Coppola, S., Ghibelli, L. (2000). GSH extrusion and and the mitochondrial pathway of apoptotic signalling. BIOCHEMICAL SOCIETY TRANSACTIONS, 28(2), 56-61.

GSH extrusion and and the mitochondrial pathway of apoptotic signalling

GHIBELLI, LINA
2000-02-01

Abstract

New evidence suggests that physiological and damaging agents activate two different pathways of apoptotic signalling, which are mediated by protein-protein interactions and mitochondrial alterations respectively. The two pathways converge at the activation of caspase 3, the key effector of the execution phase of apoptosis, thus giving similar final results. The knowledge that different biochemical routes exist allows us to re-evaluate previous apparently contradictory results concerning the events occurring during apoptosis, and their respective roles. In particular, this applies to the role of oxidative stress and redox imbalance in the signal transduction events of apoptosis. It now appears that oxidative alterations are absent, or at least unnecessary, for the development of the physiological pathway. Instead, clear indications are emerging showing that redox imbalance is required for the damage-induced mitochondrial pathway. This is suggested by the finding that the depletion of glutathione, a common event in damage-induced apoptosis, is necessary and sufficient to induce cytochrome c release, the key event of this pathway. A model is proposed with GSH efflux as the backbone of the damage-induced apoptotic pathway.
feb-2000
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13 - BIOLOGIA APPLICATA
English
Animals; Cells, Cultured; Cytochrome c Group; Glutathione; Mitochondria; Models, Biological; Oxidation-Reduction; Oxidative Stress; Signal Transduction; Apoptosis
Coppola, S., Ghibelli, L. (2000). GSH extrusion and and the mitochondrial pathway of apoptotic signalling. BIOCHEMICAL SOCIETY TRANSACTIONS, 28(2), 56-61.
Coppola, S; Ghibelli, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/170707
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