| 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
|
| Resource |
| Human and Animal Cells |
JFP-J1(RCB2309) |
