PXD001495 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol |
Description | The 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. |
HostingRepository | PRIDE |
AnnounceDate | 2015-07-31 |
AnnouncementXML | Submission_2015-08-11_01:19:12.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Friedel Drepper |
SpeciesList | scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932; |
ModificationList | deamidated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue; 6x(13)C labeled residue |
Instrument | LTQ Orbitrap; LTQ Orbitrap Elite |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2014-11-17 01:49:57 | ID requested | |
1 | 2015-07-31 04:29:46 | announced | |
⏵ 2 | 2015-08-11 01:19:13 | announced | Updated 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 affiliation | Department of Biochemistry and Functional Proteomics, Faculty of Biology and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany |
contact email | bettina.warscheid@biologie.uni-freiburg.de |
lab head | |
Friedel Drepper |
contact affiliation | AG Warscheid Biologie II Albert-Ludwigs-Universität Freiburg Schänzlestr. 1 79104 Freiburg Germany |
contact email | friedel.drepper@biologie.uni-freiburg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD001495
- Label: PRIDE project
- Name: Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol