論文 - 詳細
| RRC ID | 45585 |
|---|---|
| 著者 | Köhler F, Müller-Rischart AK, Conradt B, Rolland SG. |
| タイトル | The loss of LRPPRC function induces the mitochondrial unfolded protein response. |
| ジャーナル | Aging (Albany NY) |
| Abstract |
The inactivation of the LRPPRC gene, which has previously been associated with the neurodegenerative French Canadian Leigh Syndrome, results in a decrease in the production of mitochondria-encoded subunits of complex IV, thereby causing a reduction in complex IV activity. Previously we have shown that reducing complex IV activity triggers a compensatory and conserved mitochondrial hyperfusion response. We now demonstrate that LRPPRC knock-down in mammalian cells leads to an imbalance between mitochondria-encoded and nuclear-encoded subunits of complex IV and that this imbalance triggers the mitochondrial unfolded protein response (UPR(mt)). The inactivation of the LRPPRC-like gene mma-1 in C. elegans also induces UPR(mt), which demonstrates that this response is conserved. Furthermore, we provide evidence that mitochondrial hyperfusion and UPR(mt) are coordinated but mediated by genetically distinct pathways. We propose that in the context of LRPPRC mma-1 knock-down, mitochondrial hyperfusion helps to transiently maintain mitochondrial ATP production while UPR(mt) participates in the restoration of mitochondrial proteostasis. Mitochondrial proteostasis is not only critical in pathophysiology but also during aging, as proteotoxic stress has been shown to increase with age. Therefore, we speculate that the coordination of these two mitochondrial stress responses plays a more global role in mitochondrial proteostasis. |
| 巻・号 | 7(9) |
| ページ | 701-17 |
| 公開日 | 2015-9-1 |
| DOI | 10.18632/aging.100812 |
| PII | 100812 |
| PMID | 26412102 |
| PMC | PMC4600627 |
| MeSH | Adenosine Triphosphate / biosynthesis Aging / genetics Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism* Gene Knockdown Techniques Humans Mitochondria / genetics* Mitochondrial Proteins / genetics Mitochondrial Proteins / metabolism Neoplasm Proteins / genetics* Neoplasm Proteins / metabolism* RNA, Small Interfering / pharmacology Transfection Unfolded Protein Response / genetics* |
| IF | 4.831 |
| 引用数 | 9 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm4525 tm1133 |