Mitochondrial unfolded-protein response (Caenorhabditis elegans)

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1, 4, 73333, 62, 35226255325552NucleusMitochondrionProteinConformational Stress(Unfolded Proteins)Mitochondrial ChaperonesGSP-1HSP-60ethidium bromideATFS-1 FragmentsPHB-2ClpX-likeProtease/(K07A3.3)Unfolded ProteinseIF2-alpha(Y37E3.10)UnknownParaquatUBL-5UBL-5hsp-6DVE-1hsp-60DVE-1GCN-2ATFS-1ClpX-likeProtease/(D2030.2)translationCLPP-1HAF-1ubl-5Protein FragmentsSPG-7HSP-6Lon Protease/C34B2.653, 6translationATFS-1ATFS-1HSP-60HSP-6eIF2-alpha(Y37E3.10)translation5DVE-1UBL-536Protein Fragments


Description

hypothetical pathway based on a single review article. Input on alternatives is welcome

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Quality Tags

Ontology Terms

 

Bibliography

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  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

History

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CompareRevisionActionTimeUserComment
135406view17:36, 3 September 2024EgonwConverted to use Ensembl identifiers
117061view14:22, 16 May 2021EweitzModified title
111636view05:47, 1 September 2020EgonwModified title
107348view19:41, 26 September 2019Khansperstest
84475view19:37, 25 February 2016AlexanderPicoQuick edit to datanode annotation or property
78459view10:27, 7 January 2015MaintBotadded missing graphIds
74871view17:35, 5 May 2014CgroveChanged ATFS-1 to activating dnj-10 expression instead of inhibiting
74855view23:28, 1 May 2014CgroveCleaning up
74097view14:19, 29 March 2014EgonwReplaced an outdated HMDB identifier with the ChEBI one.
73816view01:17, 25 February 2014CgroveAdded CheBI identifier to ethidium bromide
73815view01:15, 25 February 2014CgroveConnected lines to Unfolded proteins and Protein Fragments data nodes instead of graphical cartoons
73814view01:14, 25 February 2014CgrovePeriodical save, work in progress
73487view22:59, 29 January 2014CgroveAdded "Gene Transcription" to legend
73486view22:42, 29 January 2014CgroveCleaning up legend
73485view22:39, 29 January 2014CgroveAdding legend text
73484view22:39, 29 January 2014CgrovePeriodical save, work in progress
73483view22:37, 29 January 2014CgroveEditing legend
73482view22:36, 29 January 2014CgroveAdding legend
73481view22:36, 29 January 2014CgroveCleaning up
73480view22:35, 29 January 2014CgroveCleaning up
73479view22:33, 29 January 2014CgroveCleaning up
73478view22:32, 29 January 2014CgroveCleaning up
73477view22:32, 29 January 2014CgroveCleaning up
73476view22:29, 29 January 2014CgroveCleaning up
73465view22:23, 29 January 2014CgroveCleaning up
73460view22:21, 29 January 2014CgroveCleaning up
73456view22:19, 29 January 2014CgroveTesting Save
73376view20:23, 24 January 2014CgroveCleaning up
73375view20:20, 24 January 2014CgroveCleaning up
73374view20:11, 24 January 2014CgroveCleaning up
73373view20:07, 24 January 2014CgroveCleaning up
73372view20:03, 24 January 2014CgrovePeriodical save, work in progress
73371view20:03, 24 January 2014CgroveMajor Cleaning Up
73370view19:53, 24 January 2014CgrovePeriodical save, work in progress
73369view19:43, 24 January 2014CgrovePeriodical save, work in progress
73368view19:33, 24 January 2014CgrovePeriodical save, work in progress
73147view21:18, 7 January 2014KyookOntology Term : 'PW:0000379' removed !
73146view21:18, 7 January 2014KyookOntology Term : 'stress response pathway' added !
73097view00:19, 3 January 2014KyookModified description
73096view00:19, 3 January 2014KyookModified title
73090view22:55, 2 January 2014CgroveModified description
73086view21:15, 2 January 2014Cgrovecleaning up
73040view00:55, 21 December 2013CgrovePeriodical save, work in progress
73039view00:45, 21 December 2013CgrovePeriodical save, work in progress
73038view00:33, 21 December 2013CgroveAdded references
73037view00:31, 21 December 2013CgroveCleaning up
73036view00:25, 21 December 2013CgrovePeriodical save, work in progress
73035view00:21, 21 December 2013CgroveAdded mitochondrial membrane protein transporters TIOMM-40 and TIMM-23 and reference
73034view00:15, 21 December 2013CgrovePeriodical save, work in progress
73033view00:10, 21 December 2013CgroveCleaning up

External references

DataNodes

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NameTypeDatabase referenceComment
ATFS-1 FragmentsMetaboliteCHEBI:16670 (ChEBI)
ATFS-1ProteinZC376.7 (WormBase)
CLPP-1ProteinZK970.2 (WormBase)
ClpX-like

Protease/

(D2030.2)		ProteinD2030.2 (Ensembl)
ClpX-like

Protease/

(K07A3.3)		GeneProductK07A3.3 (Ensembl)
DVE-1GeneProductZK1193.5 (WormBase)
GCN-2ProteinY81G3A.3 (WormBase)
GSP-1GeneProductF29F11.6 (WormBase) GSP-1 is an eIF2-alpha phosphatase
HAF-1ProteinC30H6.6 (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-60ProteinY22D7AL.5 (WormBase)
HSP-6ProteinC37H5.8 (WormBase)
Lon Protease/ C34B2.6GeneProductC34B2.6 (WormBase)
PHB-2ProteinT24H7.1 (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.
ParaquatMetaboliteHMDB33120 (HMDB)
Protein FragmentsMetaboliteCHEBI:16670 (ChEBI)
SPG-7ProteinY47G6A.10 (WormBase)
UBL-5ProteinF46F11.4 (WormBase)
Unfolded ProteinsProtein
Unknown
eIF2-alpha (Y37E3.10)ProteinY37E3.10 (WormBase)
ethidium bromideMetabolite
hsp-60GeneProductY22D7AL.5 (WormBase)
hsp-6GeneProductC37H5.8 (WormBase)
translationPathwayGO:0006412 (GeneOntology)
ubl-5GeneProductF46F11.4 (WormBase)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
hsp-60mim-stimulationWBInteraction000502398 (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-6mim-stimulationWBInteraction000520482 (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.
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