Reference - Detail
| RRC ID | 46263 |
|---|---|
| Author | Baker BM, Nargund AM, Sun T, Haynes CM. |
| Title | Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2. |
| Journal | PLoS Genet |
| Abstract |
Cells respond to defects in mitochondrial function by activating signaling pathways that restore homeostasis. The mitochondrial peptide exporter HAF-1 and the bZip transcription factor ATFS-1 represent one stress response pathway that regulates the transcription of mitochondrial chaperone genes during mitochondrial dysfunction. Here, we report that GCN-2, an eIF2α kinase that modulates cytosolic protein synthesis, functions in a complementary pathway to that of HAF-1 and ATFS-1. During mitochondrial dysfunction, GCN-2-dependent eIF2α phosphorylation is required for development as well as the lifespan extension observed in Caenorhabditis elegans. Reactive oxygen species (ROS) generated from dysfunctional mitochondria are required for GCN-2-dependent eIF2α phosphorylation but not ATFS-1 activation. Simultaneous deletion of ATFS-1 and GCN-2 compounds the developmental defects associated with mitochondrial stress, while stressed animals lacking GCN-2 display a greater dependence on ATFS-1 and stronger induction of mitochondrial chaperone genes. These findings are consistent with translational control and stress-dependent chaperone induction acting in complementary arms of the UPR(mt). |
| Volume | 8(6) |
| Pages | e1002760 |
| Published | 2012-1-1 |
| DOI | 10.1371/journal.pgen.1002760 |
| PII | PGENETICS-D-11-02269 |
| PMID | 22719267 |
| PMC | PMC3375257 |
| MeSH | ATP-Binding Cassette Transporters* / genetics ATP-Binding Cassette Transporters* / metabolism Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Mitochondria* / genetics Mitochondria* / metabolism Mitochondria* / pathology Molecular Chaperones Phosphorylation Protein Biosynthesis* / genetics Protein Folding Reactive Oxygen Species / metabolism Signal Transduction Stress, Physiological Transcription Factors* / genetics Transcription Factors* / metabolism Unfolded Protein Response eIF-2 Kinase / genetics eIF-2 Kinase / metabolism |
| IF | 5.175 |
| Times Cited | 156 |
| WOS Category | GENETICS & HEREDITY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 2 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4525 |