Reference - Detail
| RRC ID | 45619 |
|---|---|
| Author | Nargund AM, Fiorese CJ, Pellegrino MW, Deng P, Haynes CM. |
| Title | Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPR(mt). |
| Journal | Mol Cell |
| Abstract |
Mitochondrial diseases and aging are associated with defects in the oxidative phosphorylation machinery (OXPHOS), which are the only complexes composed of proteins encoded by separate genomes. To better understand genome coordination and OXPHOS recovery during mitochondrial dysfunction, we examined ATFS-1, a transcription factor that regulates mitochondria-to-nuclear communication during the mitochondrial UPR, via ChIP-sequencing. Surprisingly, in addition to regulating mitochondrial chaperone, OXPHOS complex assembly factor, and glycolysis genes, ATFS-1 bound directly to OXPHOS gene promoters in both the nuclear and mitochondrial genomes. Interestingly, atfs-1 was required to limit the accumulation of OXPHOS transcripts during mitochondrial stress, which required accumulation of ATFS-1 in the nucleus and mitochondria. Because balanced ATFS-1 accumulation promoted OXPHOS complex assembly and function, our data suggest that ATFS-1 stimulates respiratory recovery by fine-tuning OXPHOS expression to match the capacity of the suboptimal protein-folding environment in stressed mitochondria, while simultaneously increasing proteostasis capacity. |
| Volume | 58(1) |
| Pages | 123-33 |
| Published | 2015-4-2 |
| DOI | 10.1016/j.molcel.2015.02.008 |
| PII | S1097-2765(15)00100-8 |
| PMID | 25773600 |
| PMC | PMC4385436 |
| MeSH | Animals Base Sequence Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / genetics Cell Nucleus / metabolism* Citric Acid Cycle / genetics DNA, Mitochondrial / genetics DNA, Mitochondrial / metabolism* Genome, Helminth Genome, Mitochondrial* Mitochondria / genetics Mitochondria / metabolism* Molecular Sequence Data Oxidative Phosphorylation Protein Folding Protein Stability Protein Transport RNA, Messenger / genetics RNA, Messenger / metabolism Signal Transduction Transcription Factors / genetics Transcription Factors / metabolism* Transcription, Genetic Unfolded Protein Response |
| IF | 15.584 |
| Times Cited | 140 |
| WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| Resource | |
| C.elegans | tm4525 |