Bax does not directly participate in the Ca2+-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 Ca2+/Pi-induced permeability transition by using mitochondria isolated 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 Ca2+-retention experiments. Mitochondria from a bax-/bak- cell line also underwent an analogous Ca 2+/Pi-inducible swelling. This similarity indicates that Bax has no major role in regulating the Ca2+-induced mitochondrial permeability transition.