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Mitochondrial oxygen radical formation during reductive and oxidative stress to intact hepatocytes
1Department of Anatomy, Case Western Reserve University, Cleveland, Ohio, USA.
Abstract:
After simple respiratory inhibition, glycolytic substrates prevent cell death by providing an alternate source of cellular ATP. When mitochondrial uncoupling ensues, the uncoupler-stimulated mitochondrial ATPase hydrolyzes ATP formed by glycolysis and protection is lost. Electron transfer components abnormally reduced by respiratory inhibition, especially ubisemiquinone, react directly with oxygen to form toxic radicals. Mitochondria also generate reactive oxygen species after exposure to oxidant chemicals. A consequence is onset of the mitochondrial permeability transition, which leads to uncoupling, cellular ATP depletion and loss of viability. Thus, mitochondria are both a source and a target of toxic oxygen radicals in cell injury.
Insights
Glycolytic substrates prevent cell death by supplying ATP during respiratory inhibition. However, mitochondrial uncoupling and reactive oxygen species formation can still lead to cell injury and loss of viability.
Area of Science:
- Biochemistry
- Cell Biology
- Mitochondrial Function
Background:
- Respiratory inhibition can be overcome by glycolysis, which provides cellular ATP.
- Mitochondria play a dual role in cell injury, acting as both a source and target of toxic oxygen radicals.
Purpose of the Study:
- To investigate the mechanisms by which respiratory inhibition affects cell viability.
- To explore the role of mitochondria and reactive oxygen species in cell injury.
Main Methods:
- Cellular ATP levels were monitored under conditions of respiratory inhibition.
- Mitochondrial function and reactive oxygen species production were assessed.
- The mitochondrial permeability transition was induced and its consequences observed.
Main Results:
- Glycolytic substrates provided ATP and prevented cell death following respiratory inhibition.
- Mitochondrial uncoupling led to ATP hydrolysis and loss of protection.
- Abnormally reduced electron transfer components and oxidant chemicals induced reactive oxygen species formation.
- Mitochondrial permeability transition resulted in uncoupling, ATP depletion, and cell death.
Conclusions:
- Mitochondria are critical targets in cell injury induced by toxic oxygen radicals.
- While glycolysis can offer protection against respiratory inhibition, mitochondrial dysfunction remains a key factor in cell death.