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PXD001495

PXD001495 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMistargeted mitochondrial proteins activate a proteostatic response in the cytosol
DescriptionThe vast majority of the mitochondrial proteome originates from nuclear genes and is transported into the organelle after synthesis in the cytosol. Complex machineries, which maintain the specificity of protein import and sorting, include the TIM23 translocase responsible for the transfer of precursor proteins into the matrix and the MIA machinery required for the biogenesis of intermembrane space proteins. Dysfunctions of mitochondrial protein sorting pathways result in diminishing specific substrate proteins, followed by systemic pathology of the organelle and organismal death1-4. Cellular responses that are caused by accumulation of mitochondrial precursor proteins in the cytosol are largely unknown. Here we show a comprehensive picture of the changes in the cellular transcriptome and proteome in response to the stress associated with protein import dysfunction. We identify pathways that protect the cell against mitochondrial biogenesis defects by inhibiting protein synthesis and by activation of the proteasome, a major machine for cellular protein clearance. The proteasomal activity is modulated in proportion to the quantity of mislocalized mitochondrial precursor proteins in the cytosol. We propose that this type of unfolded protein response activated by mistargeting of proteins (UPRam) is beneficial for the cells. UPRam provides a means for buffering the consequences of physiological slowdown in mitochondrial protein import and for counteracting pathologies that are caused or contributed by mitochondrial dysfunction.
HostingRepositoryPRIDE
AnnounceDate2015-07-31
AnnouncementXMLSubmission_2015-08-11_01:19:12.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterFriedel Drepper
SpeciesList scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationListdeamidated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; 6x(13)C labeled residue
InstrumentLTQ Orbitrap; LTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02014-11-17 01:49:57ID requested
12015-07-31 04:29:46announced
22015-08-11 01:19:13announcedUpdated publication reference for PubMed record(s): 26245374.
Publication List
Wrobel L, Topf U, Bragoszewski P, Wiese S, Sztolsztener ME, Oeljeklaus S, Varabyova A, Lirski M, Chroscicki P, Mroczek S, Januszewicz E, Dziembowski A, Koblowska M, Warscheid B, Chacinska A, Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature, 524(7566):485-8(2015) [pubmed]
Keyword List
curator keyword: Biological
submitter keyword: SILAC, proteomics, mitochondria, yeast, protein transport, MIA pathway, proteasome, unfolded protein response
Contact List
Bettina Warscheid
contact affiliationDepartment of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany
contact emailbettina.warscheid@biologie.uni-freiburg.de
lab head
Friedel Drepper
contact affiliationAG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany
contact emailfriedel.drepper@biologie.uni-freiburg.de
dataset submitter
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Dataset FTP location
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