PXD029418-1

PXD029418 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-29 02:49:15	ID requested
⏵ 1	2022-01-19 03:32:58	announced

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]

submitter keyword: Leukodystrophy

Ataxia

Parkinson’s disease

HARS2, LARS2

TWNK

ERAL1

ClpB

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

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PRIDE project URI

• PRIDE
  1. PXD029418
     1. Label: PRIDE project
     2. Name: Inactivity of peptidase ClpP causes primary accumulation of mitochondrial disaggregase ClpX with its interactors at the nucleoid and RNA granule