Reference - Detail
| RRC ID | 37881 |
|---|---|
| Author | Hasegawa K, Yasuda T, Shiraishi C, Fujiwara K, Przedborski S, Mochizuki H, Yoshikawa K. |
| Title | Promotion of mitochondrial biogenesis by necdin protects neurons against mitochondrial insults. |
| Journal | Nat Commun |
| Abstract |
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-1α is a master regulator of mitochondrial biogenesis and function. Here we identify necdin as a potent PGC-1α stabilizer that promotes mitochondrial biogenesis via PGC-1α 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-1α protein are reduced. Necdin strongly stabilizes PGC-1α 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-1α to exert neuroprotection against mitochondrial insults. |
| Volume | 7 |
| Pages | 10943 |
| Published | 2016-3-14 |
| DOI | 10.1038/ncomms10943 |
| PII | ncomms10943 |
| PMID | 26971449 |
| PMC | PMC4793078 |
| MeSH | Animals Blotting, Western Cerebral Cortex / cytology DNA, Mitochondrial Disease Models, Animal Dopaminergic Neurons / metabolism* Gene Expression HEK293 Cells Humans Immunohistochemistry Immunoprecipitation Membrane Potential, Mitochondrial Mice Mice, Knockout Mitochondria / metabolism* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Nerve Tissue Proteins / genetics* Neurons / metabolism* Nuclear Proteins / genetics* Organelle Biogenesis* Parkinson Disease / genetics Parkinson Disease / metabolism Parkinsonian Disorders / genetics* Parkinsonian Disorders / metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Protein Stability Reverse Transcriptase Polymerase Chain Reaction Substantia Nigra / metabolism* Transcription Factors / metabolism* |
| IF | 12.121 |
| Times Cited | 34 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 22 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | JFP-J1(RCB2309) |