Title
Bax Supports The Mitochondrial Network, Promoting Bioenergetics In Nonapoptotic Cells
Keywords
Adenosine 5'-triphosphate; BCL-2; Homeostasis; Metabolism
Abstract
The dual functionality of the tumor suppressor BAX is implied by the nonapoptotic functions of other members of the BCL-2 family. To explore this, mitochondrial metabolism was examined in BAX-deficient HCT-116 cells as well as primary hepatocytes from BAX-deficient mice. Although mitochondrial density and mitochondrial DNA content were the same in BAX-containing and BAX-deficient cells, MitoTracker staining patterns differed, suggesting the existence of BAX-dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in BAX-deficient cells, while glycolysis was increased. These results suggested that cells lacking BAX have a deficiency in the ability to generate ATP through cellular respiration. This conclusion was supported by detection of reduced citrate synthase activity in BAX-deficient cells. In nonapoptotic cells, a portion of BAX associated with mitochondria and a sequestered, protease-resistant form was detected. Inhibition of BAX with small interfering RNAs reduced intracellular ATP content in BAX-containing cells. Expression of either full-length or COOHterminal-truncated BAX in BAX-deficient cells rescued ATP synthesis and oxygen consumption and reduced glycolytic activity, suggesting that this metabolic function of BAX was not dependent upon its COOH-terminal helix. Expression of BCL-2 in BAX-containing cells resulted in a subsequent loss of ATP measured, implying that, even under nonapoptotic conditions, an antagonistic interaction exists between the two proteins. These findings infer that a basal amount of BAX is necessary to maintain energy production via aerobic respiration. © 2011 the American Physiological Society.
Publication Date
6-2-2011
Publication Title
American Journal of Physiology - Cell Physiology
Volume
300
Issue
6
Number of Pages
-
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1152/ajpcell.00325.2010
Copyright Status
Unknown
Socpus ID
79957665553 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/79957665553
STARS Citation
Boohaker, Rebecca J.; Zhang, Ge; Carlson, Adina Loosley; Nemec, Kathleen N.; and Khaled, Annette R., "Bax Supports The Mitochondrial Network, Promoting Bioenergetics In Nonapoptotic Cells" (2011). Scopus Export 2010-2014. 2456.
https://stars.library.ucf.edu/scopus2010/2456