RT Journal Article
SR Electronic
T1 The VDAC2-BAK Rheostat Controls Thymocyte Survival
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra48
OP ra48
DO 10.1126/scisignal.2000274
VO 2
IS 85
A1 Ren, Decheng
A1 Kim, Hyungjin
A1 Tu, Ho-Chou
A1 Westergard, Todd D.
A1 Fisher, Jill K.
A1 Rubens, Jeff A.
A1 Korsmeyer, Stanley J.
A1 Hsieh, James J.-D.
A1 Cheng, Emily H.-Y.
YR 2009
UL http://stke.sciencemag.org/content/2/85/ra48.abstract
AB The proapoptotic proteins BAX and BAK constitute the mitochondrial apoptotic gateway that executes cellular demise after integrating death signals. The lethal BAK is kept in check by voltage-dependent anion channel 2 (VDAC2), a mammalian-restricted VDAC isoform. Here, we provide evidence showing a critical role for the VADC2-BAK complex in determining thymocyte survival in vivo. Genetic depletion of Vdac2 in the thymus resulted in excessive cell death and hypersensitivity to diverse death stimuli including engagement of the T cell receptor. These phenotypes were completely rescued by the concurrent deletion of Bak but not that of Bax. Thus, the VDAC2-BAK axis provides a mechanism that governs the homeostasis of thymocytes. Our study reveals a sophisticated built-in rheostat that likely fine-tunes immune competence to balance autoimmunity and immunodeficiency.