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Updated: Aug 26, 2026

Assessment of Open Probability of the Mitochondrial Permeability Transition Pore in the Setting of Coenzyme Q Excess
Published on: June 1, 2022
Mitochondrial permeability transition induced by reactive oxygen species is independent of cholesterol-regulated
Anna Colell1, Carmen García-Ruiz, Montserrat Mari
1Institut de Malalties Digestives, Hospital Clínic y Provincial, Instituto Investigaciones Biomédicas August Pi Suñer, C/Villarroel 170, 08036 Barcelona, Spain.
Abstract:
Cholesterol enrichment of rat liver mitochondria (CHM) impairs atractyloside-induced mitochondrial permeability transition (MPT) due to decreased membrane fluidity. In this study we addressed the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS). Superoxide anion generated by xanthine plus xanthine oxidase triggered mitochondrial swelling and cytochrome c release in CHM, which was prevented by butylated hydroxytoluene, an anti-voltage-dependent anion channel antibody, or cyclosporin A. Furthermore, hydrogen peroxide generated by the combination of ganglioside GD3 and mitochondrial GSH depletion elicited mitochondrial swelling and release of cytochrome c, Smac/Diablo and apoptosis-inducing factor in control mitochondria and CHM. Thus, ROS induce MPT and apoptosome activation regardless of decreased mitochondrial membrane dynamics due to cholesterol enrichment.
Insights
Cholesterol enrichment impairs mitochondrial permeability transition (MPT) induced by atractyloside but not reactive oxygen species (ROS). ROS trigger MPT and apoptosis even in cholesterol-enriched mitochondria, indicating ROS-induced MPT is independent of membrane fluidity.
Area of Science:
- Mitochondrial biology
- Cellular signaling
- Biochemistry
Background:
- Cholesterol enrichment of rat liver mitochondria (CHM) decreases membrane fluidity.
- This reduced fluidity impairs atractyloside-induced mitochondrial permeability transition (MPT).
Purpose of the Study:
- To investigate the effect of cholesterol enrichment on MPT induced by reactive oxygen species (ROS).
Main Methods:
- Induction of MPT using superoxide anion (xanthine/xanthine oxidase) and hydrogen peroxide (ganglioside GD3/GSH depletion).
- Assessment of mitochondrial swelling and release of apoptotic factors (cytochrome c, Smac/Diablo, apoptosis-inducing factor).
- Inhibition studies using butylated hydroxytoluene, anti-VDAC antibody, and cyclosporin A.
Main Results:
- Superoxide anion triggered mitochondrial swelling and cytochrome c release in CHM, inhibited by antioxidants, anti-VDAC antibody, and cyclosporin A.
- Hydrogen peroxide induced mitochondrial swelling and release of multiple apoptotic factors in both control and CHM.
- ROS-induced MPT and apoptosome activation occurred irrespective of cholesterol-induced changes in mitochondrial membrane dynamics.
Conclusions:
- Reactive oxygen species (ROS) induce MPT and subsequent apoptosis signaling pathways.
- ROS-induced MPT is independent of mitochondrial membrane fluidity alterations caused by cholesterol enrichment.
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