Mitochondrial unfolded-protein response (Caenorhabditis elegans)

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Bibliography

1. Broadley SA, Hartl FU; ''Mitochondrial stress signaling: a pathway unfolds.''; Trends Cell Biol, 2008 PubMed Europe PMC Scholia
2. Haynes CM, Ron D; ''The mitochondrial UPR - protecting organelle protein homeostasis.''; J Cell Sci, 2010 PubMed Europe PMC Scholia
3. Pellegrino MW, Nargund AM, Haynes CM; ''Signaling the mitochondrial unfolded protein response.''; Biochim Biophys Acta, 2013 PubMed Europe PMC Scholia
4. 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
5. 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
6. 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
7. 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
8. 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
9. 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

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External references

DataNodes

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
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.