title: Bax does not directly participate in the Ca(2+)-induced permeability transition of isolated mitochondria.
abstract: The mitochondrial permeability transition pore and Bax have both been proposed to be involved in the release of pro-apoptotic factors from mitochondria in the "intrinsic" pathway of apoptosis. The permeability transition pore is widely thought to be a supramolecular complex including or interacting with Bax. Given the relevance of the permeability transition in vivo, we have verified whether Bax influences the formation and/or the properties of the Ca(2+)/P(i)-induced permeability transition by using mitochondriaisolated from isogenic human colon cancer bax(+/-) and bax(-/-) HCT116 cell lines. We used mitochondria isolated from both types of cells and from Bax(+) cells exposed to apoptotic stimuli, as well as Bax-less mitochondria into which exogenous Bax had been incorporated. All exhibited the same behavior and pharmacological profile in swelling and Ca(2+)-retention experiments. Mitochondria from a bax(-)/bak(-) cell line also underwent an analogous Ca(2+)/P(i)-inducible swelling. This similarity indicates that Bax hasno major role in regulating the Ca(2+)-induced mitochondrial permeability transition.
authors.affiliation: CNR Institute of Neuroscience, Biomembranes Section and Department of Biomedical Sciences, University of Padova, Padova, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: De Marchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Campello
authors.forename: Ildikò
authors.initials: I
authors.lastname: Szabò
authors.forename: Francesco
authors.initials: F
authors.lastname: Tombola
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Martinou
authors.forename: Mario
authors.initials: M
authors.lastname: Zoratti
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein
chemical_list: C494826:BAX protein, human; C494827:Bax protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D002118:Calcium