| First Author | Wang Z | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 10 | Pages | 1916-24 |
| PubMed ID | 23459946 | Mgi Jnum | J:203748 |
| Mgi Id | MGI:5528620 | Doi | 10.1128/MCB.00015-13 |
| Citation | Wang Z, et al. (2013) Nucleophosmin, a critical Bax cofactor in ischemia-induced cell death. Mol Cell Biol 33(10):1916-24 |
| abstractText | We hypothesized that nucleophosmin (NPM), a nucleolar phosphoprotein, is critical for Bax-mediated cell death. To test this hypothesis, Bax activation was induced by metabolic stress. During stress, nucleolar NPM translocated into the cytosol, NPM-Bax complexes formed, and both NPM and Bax accumulated in mitochondria. Expression of a cytosol-restricted NPM mutant (NPM-DeltaNLS), but not a nucleus-restricted NPM mutant, increased NPM-Bax complex formation, mitochondrial NPM and Bax accumulation, mitochondrial membrane injury, caspase 3 activation, and ischemia-induced cell death. Coexpression of NPM-DeltaNLS with constitutively active Bax mutants caused nearly universal cell death in the absence of metabolic stress, whereas expression of active Bax or NPM-DeltaNLS alone did not. A Bax peptide that disrupts NPM-Bax interaction significantly reduced cell death caused by exposure to metabolic inhibitors in vitro and preserved kidney function after ischemia in vivo. Thus, NPM-Bax interaction enhances mitochondrial Bax accumulation, organelle injury, and cell death. NPM-Bax complex formation is a novel target for preventing ischemic tissue injury. |
