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Published on: May 24, 2024
Effects of alpha-mangostin on mitochondrial energetic metabolism
E Martínez-Abundis1, N García, F Correa
1Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1., Col. Sección XVI, Mexico 14080, D.F., Mexico.
Abstract:
Although alpha-mangostin prevents from toxicity associated to oxidative stress, it also promotes apoptotic cell death in cancer cells. Such effects have been associated with mitochondrial membrane depolarization and cytochrome c release. Therefore, the aim of this work was to analyze the potentially harmful effect of this natural compound on relevant parameters of mitochondrial function from normal tissue. Our results showed that alpha-mangostin protected mitochondria from peroxidative damage, but at high concentration, it acted as an uncoupler, reduced dramatically ADP-stimulated respiration and inhibited the activity of respiratory complex IV, making mitochondria prone to permeability transition, which is a mitochondrial player on cell fate.
Insights
Alpha-mangostin protects normal mitochondria from oxidative damage but can harm them at high concentrations. It disrupts mitochondrial respiration and increases susceptibility to cell death pathways.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Alpha-mangostin exhibits antioxidant properties and induces apoptosis in cancer cells.
- These effects are linked to mitochondrial membrane depolarization and cytochrome c release.
- Investigating the impact of alpha-mangostin on normal mitochondria is crucial.
Purpose of the Study:
- To evaluate the effects of alpha-mangostin on mitochondrial function in normal tissues.
- To determine potential toxicity of alpha-mangostin to mitochondria.
Main Methods:
- Mitochondrial function assays
- Assessment of oxidative stress parameters
- Analysis of respiratory complex activity
Main Results:
- Alpha-mangostin demonstrated protective effects against peroxidative damage in mitochondria.
- At high concentrations, alpha-mangostin acted as an uncoupler, significantly reducing ADP-stimulated respiration.
- Inhibition of respiratory complex IV activity and increased susceptibility to permeability transition were observed.
Conclusions:
- Alpha-mangostin exhibits a dual role, protecting against oxidative stress but potentially inducing toxicity in normal mitochondria at high doses.
- The compound's effects on mitochondrial respiration and integrity warrant further investigation for therapeutic applications.
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