論文 - 詳細
| RRC ID | 53299 |
|---|---|
| 著者 | Fiorese CJ, Schulz AM, Lin YF, Rosin N, Pellegrino MW, Haynes CM. |
| タイトル | The Transcription Factor ATF5 Mediates a Mammalian Mitochondrial UPR. |
| ジャーナル | Curr Biol |
| Abstract |
Mitochondrial dysfunction is pervasive in human pathologies such as neurodegeneration, diabetes, cancer, and pathogen infections as well as during normal aging. Cells sense and respond to mitochondrial dysfunction by activating a protective transcriptional program known as the mitochondrial unfolded protein response (UPR(mt)), which includes genes that promote mitochondrial protein homeostasis and the recovery of defective organelles [1, 2]. Work in Caenorhabditis elegans has shown that the UPR(mt) is regulated by the transcription factor ATFS-1, which is regulated by organelle partitioning. Normally, ATFS-1 accumulates within mitochondria, but during respiratory chain dysfunction, high levels of reactive oxygen species (ROS), or mitochondrial protein folding stress, a percentage of ATFS-1 accumulates in the cytosol and traffics to the nucleus where it activates the UPR(mt) [2]. While similar transcriptional responses have been described in mammals [3, 4], how the UPR(mt) is regulated remains unclear. Here, we describe a mammalian transcription factor, ATF5, which is regulated similarly to ATFS-1 and induces a similar transcriptional response. ATF5 expression can rescue UPR(mt) signaling in atfs-1-deficient worms requiring the same UPR(mt) promoter element identified in C. elegans. Furthermore, mammalian cells require ATF5 to maintain mitochondrial activity during mitochondrial stress and promote organelle recovery. Combined, these data suggest that regulation of the UPR(mt) is conserved from worms to mammals. |
| 巻・号 | 26(15) |
| ページ | 2037-2043 |
| 公開日 | 2016-8-8 |
| DOI | 10.1016/j.cub.2016.06.002 |
| PII | S0960-9822(16)30614-5 |
| PMID | 27426517 |
| PMC | PMC4980197 |
| MeSH | Activating Transcription Factors / genetics* Activating Transcription Factors / metabolism Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / metabolism Caenorhabditis elegans / genetics* Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism HEK293 Cells HeLa Cells Humans Mitochondrial Proteins / genetics* Mitochondrial Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism Unfolded Protein Response |
| IF | 9.601 |
| 引用数 | 166 |
| 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 | 11 |
| 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 |