PXD029418 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Inactivity of peptidase ClpP causes primary accumulation of mitochondrial disaggregase ClpX with its interactors at the nucleoid and RNA granule |
Description | Mitochondrial matrix peptidase ClpP inactivating mutations in human cause an autosomal recessive Perrault syndrome variant (PRLTS3), characterized by ovarian failure with early sensorineural deafness, often followed by general neurodegeneration. Mouse models showed that accumulations of (i) its main protein interactor, the substrate-selecting AAA+ ATPase ClpX, (ii) mitoribosomes, and (iii) mtDNA nucleoids are main cellular consequences of ClpP mutations. However, the sequence of these events and their validity in human remain unclear. Here, we studied global proteome profiles to define ClpP substrates among mitochondrial ClpX interactors, which accumulated consistently in ClpP-null mouse embryonal fibroblasts and brain. Validation work included novel ClpP-mutant patient fibroblast proteomics. ClpX co-accumulated in mitochondria with POLDIP2 as nucleoid component, LRPPRC as mitochondrial poly(A) mRNA granule element, GFM1 (in mouse also GRSF1) as tRNA processing factors. Only in mouse, accumulated ClpX, GFM1 and GRSF1 appeared in nuclear fractions. Mitoribosomal accumulation was minor. Consistent accumulations in murine and human fibroblasts also affected multimerizing factors not known as ClpX interactors, namely OAT, ASS1, ACADVL, STOM, PRDX3, PC, MUT, ALDH2, PMPCB, UQCRC2 and ACADSB, but the impact on downstream metabolites was marginal. Our data demonstrate the primary impact of ClpXP on the assembly of proteins with nucleic acids, and show nucleoid enlargement in human as key consequence. |
HostingRepository | PRIDE |
AnnounceDate | 2022-01-19 |
AnnouncementXML | Submission_2022-01-19_03:32:57.979.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Nina Bach |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | methionine oxidation with neutral loss of 64 Da; mono N-acetylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-10-29 02:49:15 | ID requested | |
⏵ 1 | 2022-01-19 03:32:58 | announced | |
Publication List
Key J, Torres-Odio S, Bach NC, Gispert S, Koepf G, Reichlmeir M, West AP, Prokisch H, Freisinger P, Newman WG, Shalev S, Sieber SA, Wittig I, Auburger G, Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA. Cells, 10(12):(2021) [pubmed] |
Keyword List
submitter keyword: Leukodystrophy |
Ataxia |
Parkinson’s disease |
HARS2, LARS2 |
TWNK |
ERAL1 |
ClpB |
Contact List
Stephan A. Sieber |
contact affiliation | TU Munich, Chair of Organic Chemistry II, Center for Protein Assemblies, Ernst-Otto-Fischer-Str. 8 85748 Garching |
contact email | stephan.sieber@tum.de |
lab head | |
Nina Bach |
contact affiliation | TU München |
contact email | nina.bach@tum.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD029418
- Label: PRIDE project
- Name: Inactivity of peptidase ClpP causes primary accumulation of mitochondrial disaggregase ClpX with its interactors at the nucleoid and RNA granule