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Mitochondrial permeability transition induced by chemically generated singlet oxygen.
Ricardo G Cosso1, Jussiani Turim, Iseli L Nantes
1Departamento de Patologia Clínica, Faculdade de Ciências Médicas, NMCE, Universidade Estadual de Campinas, São Paulo, Brazil.
Journal of Bioenergetics and Biomembranes
|August 13, 2002
Summary
Singlet oxygen (1O2) triggers mitochondrial permeability transition by oxidizing protein thiols. This process, studied using NDPO2 in isolated rat liver mitochondria, is inhibited by specific agents and enhanced by deuterium oxide.
Area of Science:
- Biochemistry
- Mitochondrial Physiology
- Oxidative Stress
Background:
- Mitochondria are crucial for cellular energy production.
- Singlet oxygen (1O2) is a reactive oxygen species implicated in cellular damage.
- The mechanisms of 1O2-induced mitochondrial dysfunction are not fully understood.
Purpose of the Study:
- To investigate the effect of chemically generated singlet oxygen (1O2) on isolated rat liver mitochondria.
- To elucidate the role of mitochondrial permeability transition (MPT) in 1O2-induced damage.
- To identify the molecular targets of 1O2 in mitochondrial membranes.
Main Methods:
- Isolated rat liver mitochondria were treated with 3,3'-(1,4-naphthylidene) dipropionate endoperoxide (NDPO2) to generate 1O2.
- Mitochondrial respiration and transmembrane potential (deltapsi) were measured.
- The effects of MPT inhibitors (EGTA, dithiothreitol, ADP, cyclosporin A) and deuterium oxide (D2O) were assessed.
- Oxidation of membrane protein thiols was monitored.
Main Results:
- 1O2 inhibited mitochondrial respiration except when using TMPD/ascorbate.
- NDPO2 treatment led to a time-dependent decrease in deltapsi, indicative of MPT.
- MPT induction was sensitive to known inhibitors and enhanced by D2O.
- 1O2-induced permeabilization correlated with oxidation of membrane protein thiols.
Conclusions:
- Chemically generated singlet oxygen induces mitochondrial permeability transition in isolated rat liver mitochondria.
- The MPT is mediated by the oxidation of membrane protein thiols.
- These findings highlight a novel mechanism of oxidative damage to mitochondria by singlet oxygen.