| First Author | Ren D | Year | 2009 |
| Journal | Sci Signal | Volume | 2 |
| Issue | 85 | Pages | ra48 |
| PubMed ID | 19706873 | Mgi Jnum | J:220951 |
| Mgi Id | MGI:5637497 | Doi | 10.1126/scisignal.2000274 |
| Citation | Ren D, et al. (2009) The VDAC2-BAK rheostat controls thymocyte survival. Sci Signal 2(85):ra48 |
| abstractText | 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. |
