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PXD022521-1

PXD022521 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleHuman mitochondrial protein import proteomics
DescriptionMost mitochondrial proteins are encoded in the nucleus and require mitochondrial import after translation in the cytosol. A number of mutations in the mitochondrial protein import machinery have been shown to lead to human pathologies. However, a lack suitable tools to measure mitochondrial protein uptake has prevented determination of import rates across the mitochondrial proteome and identification of specific proteins affected by perturbation. Here, we introduce a pulsed-SILAC based proteomics approach that includes a booster signal to selectively increase the sensitivity for mitochondrial proteins, enabling dynamic analysis of mitochondrial protein uptake at the global scale. We applied this method to determine protein uptake kinetics and examined how inhibitors of different mitochondrial import machineries affect protein uptake in sub-mitochondrial compartments. Monitoring changes in translation and protein uptake upon mitochondrial membrane depolarization revealed that protein uptake was extensively modulated the import- and translation machineries, via activation of the integrated stress response. Strikingly, uptake changes were not uniform with three groups of protein identified that showed no changes in uptake, or changes driven by reduced translation or import capacity. This study provides with a quantitative proteomics method to monitor mitochondrial protein uptake at a global scale to provide with insight into uptake rearrangements upon perturbation.
HostingRepositoryPRIDE
AnnounceDate2021-12-18
AnnouncementXMLSubmission_2021-12-17_17:22:56.876.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSüleyman Bozkurt
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue; isotope labeled residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-11-13 07:10:28ID requested
12021-12-17 17:22:58announced
Publication List
Schäfer JA, Bozkurt S, Michaelis JB, Klann K, Münch C, Global mitochondrial protein import proteomics reveal distinct regulation by translation and translocation machinery. Mol Cell, 82(2):435-446.e7(2022) [pubmed]
Keyword List
submitter keyword: human, mePROD, TMT, pulsed SILAC, mitochondrial import
Contact List
Christian Münch
contact affiliationInstitute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany Frankfurt Cancer Institute, Frankfurt am Main, Germany Cardio-Pulmonary Institute, Frankfurt am Main, Germany
contact emailch.muench@em.uni-frankfurt.de
lab head
Süleyman Bozkurt
contact affiliationInstitute of Biochemistry II, Goethe University Frankfurt, Theodor-Stern-Kai 7, Haus 75 60590 Frankfurt am Main
contact emailbozkurt@med.uni-frankfurt.de
dataset submitter
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