BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells
Abbreviated Journal Title
Am. J. Physiol.-Cell Physiol.
metabolism; adenosine 5 '-triphosphate; homeostasis; BCL-2; BCL-2 FAMILY; CYTOCHROME-C; DEFICIENT MICE; APOPTOSIS; DEATH; PROTEINS; DOMAIN; MEMBRANE; BH2; HETERODIMERIZES; Cell Biology; Physiology
Boohaker RJ, Zhang G, Carlson AL, Nemec KN, Khaled AR. BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells. Am J Physiol Cell Physiol 300: C1466-C1478, 2011. First published February 2, 2011; doi: 10.1152/ajpcell.00325.2010.-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 COOH-terminal-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.
American Journal of Physiology-Cell Physiology
"BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells" (2011). Faculty Bibliography 2010s. 1110.