| First Author | Park SJ | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 4 | Pages | 2195-204 |
| PubMed ID | 24324263 | Mgi Jnum | J:329610 |
| Mgi Id | MGI:6862514 | Doi | 10.1074/jbc.M113.492587 |
| Citation | Park SJ, et al. (2014) Down-regulation of mortalin exacerbates Abeta-mediated mitochondrial fragmentation and dysfunction. J Biol Chem 289(4):2195-204 |
| abstractText | Mitochondrial dynamics greatly influence the biogenesis and morphology of mitochondria. Mitochondria are particularly important in neurons, which have a high demand for energy. Therefore, mitochondrial dysfunction is strongly associated with neurodegenerative diseases. Until now various post-translational modifications for mitochondrial dynamic proteins and several regulatory proteins have explained complex mitochondrial dynamics. However, the precise mechanism that coordinates these complex processes remains unclear. To further understand the regulatory machinery of mitochondrial dynamics, we screened a mitochondrial siRNA library and identified mortalin as a potential regulatory protein. Both genetic and chemical inhibition of mortalin strongly induced mitochondrial fragmentation and synergistically increased Abeta-mediated cytotoxicity as well as mitochondrial dysfunction. Importantly we determined that the expression of mortalin in Alzheimer disease (AD) patients and in the triple transgenic-AD mouse model was considerably decreased. In contrast, overexpression of mortalin significantly suppressed Abeta-mediated mitochondrial fragmentation and cell death. Taken together, our results suggest that down-regulation of mortalin may potentiate Abeta-mediated mitochondrial fragmentation and dysfunction in AD. |
