| First Author | Hasegawa K | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10943 | PubMed ID | 26971449 |
| Mgi Jnum | J:236559 | Mgi Id | MGI:5806378 |
| Doi | 10.1038/ncomms10943 | Citation | Hasegawa K, et al. (2016) Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. Nat Commun 7:10943 |
| abstractText | Neurons rely heavily on mitochondria for their function and survival. Mitochondrial dysfunction contributes to the pathogenesis of neurodegenerative diseases such as Parkinson's disease. PGC-1alpha is a master regulator of mitochondrial biogenesis and function. Here we identify necdin as a potent PGC-1alpha stabilizer that promotes mitochondrial biogenesis via PGC-1alpha in mammalian neurons. Expression of genes encoding mitochondria-specific proteins decreases significantly in necdin-null cortical neurons, where mitochondrial function and expression of the PGC-1alpha protein are reduced. Necdin strongly stabilizes PGC-1alpha by inhibiting its ubiquitin-dependent degradation. Forced expression of necdin enhances mitochondrial function in primary cortical neurons and human SH-SY5Y neuroblastoma cells to prevent mitochondrial respiratory chain inhibitor-induced degeneration. Moreover, overexpression of necdin in the substantia nigra in vivo of adult mice protects dopaminergic neurons against degeneration in experimental Parkinson's disease. These data reveal that necdin promotes mitochondrial biogenesis through stabilization of endogenous PGC-1alpha to exert neuroprotection against mitochondrial insults. |
