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Mitochondrial permeability transition and oxidative stress
A J Kowaltowski1, R F Castilho, A E Vercesi
1Departamento de Bioquímica, Instituto de Quimica, Universidade de São Paulo, São Paulo, SP, Brazil.
Abstract:
Mitochondrial permeability transition (MPT) is a non-selective inner membrane permeabilization that may precede necrotic and apoptotic cell death. Although this process has a specific inhibitor, cyclosporin A, little is known about the nature of the proteinaceous pore that results in MPT. Here, we review data indicating that MPT is not a consequence of the opening of a pre-formed pore, but the consequence of oxidative damage to pre-existing membrane proteins.
Insights
Mitochondrial permeability transition (MPT) involves inner membrane permeabilization during cell death. New evidence suggests MPT results from oxidative damage to proteins, not a pre-formed pore.
Area of Science:
- Cell Biology
- Biochemistry
- Mitochondrial Function
Background:
- Mitochondrial permeability transition (MPT) is a critical event in cell death pathways.
- MPT involves non-selective inner membrane permeabilization preceding necrosis and apoptosis.
- Cyclosporin A is a known inhibitor of MPT, but the pore's nature remains unclear.
Purpose of the Study:
- To review current data on the mechanism of MPT.
- To elucidate the molecular basis of the proteinaceous pore involved in MPT.
- To challenge the existing model of MPT pore formation.
Main Methods:
- Literature review of existing studies on MPT.
- Analysis of data related to mitochondrial inner membrane permeabilization.
- Evaluation of the role of oxidative stress in MPT.
Main Results:
- Evidence suggests MPT is not caused by the opening of a pre-formed pore.
- MPT appears to be a consequence of oxidative damage to existing membrane proteins.
- This challenges the traditional view of MPT pore formation.
Conclusions:
- The mechanism of MPT involves oxidative damage to membrane proteins.
- This understanding refines the model of cell death.
- Further research into protein damage in MPT is warranted.