Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress

Tsyregma Li, Tatiana Brustovetsky, Bruno Antonsson, Nikolai Broustovetski

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In the present study, we investigated the mechanism of cytochrome c release from isolated brain mitochondria induced by recombinant oligomeric BAX (BAXoligo). We found that BAXoligo caused a complete release of cytochrome c in a concentration- and time-dependent manner. The release was similar to those induced by alamethicin, which causes maximal mitochondrial swelling and eliminates barrier properties of the OMM. BAXoligo also produced large amplitude mitochondrial swelling as judged by light scattering assay and transmission electron microscopy. In addition, BAXoligo resulted in a strong mitochondrial depolarization. ATP or a combination of cyclosporin A and ADP, inhibitors of the mPT, suppressed BAXoligo-induced mitochondrial swelling and depolarization as well as cytochrome c release but did not influence BAXoligo insertion into the OMM. Both BAXoligo- and alamethicin-induced cytochrome c releases were accompanied by inhibition of ROS generation, which was assessed by measuring mitochondrial H2O2 release with an Amplex Red assay. The mPT inhibitors antagonized suppression of ROS generation caused by BAXoligo but not by alamethicin. Thus, BAXoligo resulted in a complete cytochrome c release from isolated brain mitochondria in the mPT-dependent manner without involvement of oxidative stress by the mechanism requiring mitochondrial remodeling and permeabilization of the OMM.

Original languageEnglish
Pages (from-to)1409-1421
Number of pages13
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1777
Issue number11
DOIs
StatePublished - Nov 2008

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Oxidative stress
Cytochromes c
Alamethicin
Permeability
Mitochondrial Swelling
Oxidative Stress
Swelling
Mitochondria
Depolarization
Assays
Brain
Transmission Electron Microscopy
Light scattering
Adenosine Diphosphate
Cyclosporine
Adenosine Triphosphate
Transmission electron microscopy
Light

Keywords

  • Apoptosis
  • BAX
  • Brain
  • Calcium
  • Mitochondria
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Cite this

Oligomeric BAX induces mitochondrial permeability transition and complete cytochrome c release without oxidative stress. / Li, Tsyregma; Brustovetsky, Tatiana; Antonsson, Bruno; Broustovetski, Nikolai.

In: Biochimica et Biophysica Acta - Bioenergetics, Vol. 1777, No. 11, 11.2008, p. 1409-1421.

Research output: Contribution to journalArticle

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