Abstract 3794: BAX maintains mitochondrial bioenergetics in colon cancer cells

The dual functionality of the tumor suppressor, BAX, is implied by the non-apoptotic functions of other pro-apoptotic BCL-2 family proteins. To explore this, the mitochondrial morphology and ATP producing capability in both BAX-containing and BAX-deficient HCT-116 colon cancer cells were examined. While BAX deficient cells maintain the same mitochondrial mass as their BAX containing counterparts, these mitochondria were visibly smaller, more compact, and unable to maintain an organized network. Oxygen consumption and ATP levels were also reduced in these cells, a phenomenon that was replicated upon treatment of BAX-containing cells with the uncoupling agent, FCCP. These results, coupled with a marked decrease in citrate synthase activity, suggested that cells lacking BAX have a deficiency in the ability to generate ATP through oxidative phosphorylation. Inhibition of endogenous BAX through treatment with small interfering RNAs reinforced the necessity of BAX activity in the maintenance of aerobic respiration and the production of ATP. An examination of the localization of full length and C-terminal truncated BAX in non-apoptotic, BAX deficient cells, indicated that a small fraction of the existing cytosolic BAX is needed at the mitochondrial membrane to maintain ATP production. However, this function is not dependent upon the C-terminal helix. Co-expression of BAX and BCL-2 resulted in a subsequent loss of ATP production, implying that, even under non-apoptotic conditions, an antagonistic interaction exists between the two proteins. These findings infer that a basal amount of BAX associated with the mitochondria is necessary to maintain mitochondrial bioenergetics. The discovery of this novel, non-apoptotic role for BAX in the maintenance of ATP synthesis and suggests that complete abrogation of BAX would be detrimental to cancer cells dependent on energy production via aerobic respiration. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3794. doi:10.1158/1538-7445.AM2011-3794