Mitochondrial unfolded-protein response (Caenorhabditis elegans)
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Description
"Mitochondria are required for numerous essential metabolic processes including the regulation of apoptosis; therefore, proper maintenance of the mitochondrial proteome is crucial. The protein-folding environment in mitochondria is challenged by organelle architecture, the presence of reactive oxygen species and the difficulties associated with assembly of the electron transport chain, which consists of components encoded by both the mitochondrial and the nuclear genomes. Mitochondria have dedicated molecular chaperones and proteases that promote proper protein folding, complex assembly and quality control. Work in cultured mammalian cells and Caenorhabditis elegans has yielded clues to the mechanisms linking perturbations in the protein-folding environment in the mitochondrial matrix to the expression of nuclear genes encoding mitochondrial proteins. Here, we review the current knowledge of this mitochondrial unfolded protein response (UPRmt), compare it with the better understood UPR of the endoplasmic reticulum and highlight its potential impact on development and disease." (Haynes and Ron 2010)
Quality Tags
Ontology Terms
Saving...Bibliography
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- Broadley SA, Hartl FU; ''Mitochondrial stress signaling: a pathway unfolds.''; Trends Cell Biol, 2008 PubMed Europe PMC Scholia
- Haynes CM, Ron D; ''The mitochondrial UPR - protecting organelle protein homeostasis.''; J Cell Sci, 2010 PubMed Europe PMC Scholia
- Pellegrino MW, Nargund AM, Haynes CM; ''Signaling the mitochondrial unfolded protein response.''; Biochim Biophys Acta, 2013 PubMed Europe PMC Scholia
- Haynes CM, Petrova K, Benedetti C, Yang Y, Ron D; ''ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans.''; Dev Cell, 2007 PubMed Europe PMC Scholia
- Yoneda T, Benedetti C, Urano F, Clark SG, Harding HP, Ron D; ''Compartment-specific perturbation of protein handling activates genes encoding mitochondrial chaperones.''; J Cell Sci, 2004 PubMed Europe PMC Scholia
- Baker BM, Nargund AM, Sun T, Haynes CM; ''Protective coupling of mitochondrial function and protein synthesis via the eIF2α kinase GCN-2.''; PLoS Genet, 2012 PubMed Europe PMC Scholia
- Haynes CM, Yang Y, Blais SP, Neubert TA, Ron D; ''The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376.7 in C. elegans.''; Mol Cell, 2010 PubMed Europe PMC Scholia
- Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM; ''Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.''; Science, 2012 PubMed Europe PMC Scholia
- Benedetti C, Haynes CM, Yang Y, Harding HP, Ron D; ''Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response.''; Genetics, 2006 PubMed Europe PMC Scholia
History
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External references
DataNodes
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| Name | Type | Database reference | Comment |
|---|---|---|---|
| ATFS-1 Fragments | Metabolite | CHEBI:16670 (ChEBI)  | |
| ATFS-1 | Protein | ZC376.7 (WormBase) | |
| CLPP-1 | Protein | ZK970.2 (WormBase) | |
| ClpX-like
Protease/ (D2030.2) | Protein | D2030.2 (Ensembl) | |
| ClpX-like
Protease/ (K07A3.3) | GeneProduct | K07A3.3 (Ensembl) | |
| DVE-1 | GeneProduct | ZK1193.5 (WormBase) | |
| GCN-2 | Protein | Y81G3A.3 (WormBase) | |
| GSP-1 | GeneProduct | F29F11.6 (WormBase) | gsp-1 encodes a protein phosphatase homologous to the yeast phosphatase required for eIF2-alpha dephosphorylation. |
| HAF-1 | Protein | C30H6.6 (WormBase) | haf-1, a gene encoding a mitochondria-localized ATP-binding cassestte protein, is required for signaling within the mitochondrial unfolded protein response (UPTmt) and for coping with misfolded protein stress. Peptide efflux from isolated mitochondria was ATP dependent and required HAF-1 and the protease ClpP. |
| HSP-60 | Protein | Y22D7AL.5 (WormBase) | |
| HSP-6 | Protein | C37H5.8 (WormBase) | |
| Lon Protease/ C34B2.6 | GeneProduct | C34B2.6 (WormBase) | |
| PHB-2 | Protein | T24H7.1 (WormBase) | PHB-2, along with PHB-1, forms the mitochondrial inner membrane Prohibitin complex which is implicated in assembly of components of the respiratory chain. |
| Paraquat | Metabolite | HMDB33120 (HMDB) | |
| Protein Fragments | Metabolite | CHEBI:16670 (ChEBI) | |
| Reactive Oxygen Species?? | |||
| SPG-7 | Protein | Y47G6A.10 (WormBase) | |
| TIMM-23 | GeneProduct | 173041 (Entrez Gene) | |
| TOMM-40 | Protein | C18E9.6 (WormBase) | |
| UBL-5 | Protein | F46F11.4 (WormBase) | |
| Unfolded Proteins | Protein | ||
| dnj-10 | GeneProduct | F22B7.5 (WormBase) | |
| eIF2-alpha (Y37E3.10) | Protein | Y37E3.10 (WormBase) | |
| ethidium bromide | Metabolite | ||
| hsp-60 | GeneProduct | Y22D7AL.5 (WormBase) | |
| hsp-6 | GeneProduct | C37H5.8 (WormBase) | |
| translation | Pathway | GO:0006412 (GeneOntology) | |
| ubl-5 | GeneProduct | F46F11.4 (WormBase) |
Annotated Interactions
| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| hsp-60 | mim-stimulation | WBInteraction000502398 (WormBase) | RNAi knockdown of dve-1 prevents expression of a Phsp-60::GFP reporter transgene in response to the zc32 allele at 25 degrees Celsius, spg-7 RNAi, or exposure to Ethidium Bromide (all known to induce UPRmt and, hence, hsp-60 expression). dve-1 RNAi also disrupts induction of endogenous hsp-60 expression induced by spg-7 RNAi, as determined by QRT-PCR. ubl-5 RNAi results in diminished expression of an hsp-60::GFP reporter and endogenous hsp-60. | |
| hsp-6 | mim-stimulation | WBInteraction000520482 (WormBase) | ubl-5 RNAi results in diminished expression of an hsp-6::GFP reporter and endogenous hsp-6. dve-1 RNAi also disrupts induction of endogenous hsp-6 expression induced by spg-7 RNAi, as determined by QRT-PCR. |
