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.

FEBS Letters
|February 28, 2004
PubMed

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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