PXD042313

PXD042313 is an original dataset announced via ProteomeXchange.

Title	CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex
Description	CLPB is a mitochondrial intermembrane space AAA+ domain–containing disaggregase. CLPB mutations are associated with 3-methylglutaconic aciduria and neutropenia; however, the molecular mechanism underscoring disease and the contribution of CLPB substrates to disease pathology remains unknown. Interactions between CLPB and mitochondrial quality control (QC) factors, including PARL and OPA1, have been reported, hinting at dysregulation of organelle QC in disease. Utilizing proteomic and biochemical approaches, we define a stress-specific aggregation phenotype in a CLPB-null environment and define the CLPB substrate profile. We show an interplay between intermembrane space proteins including CLPB, HAX1, HTRA2, and the inner membrane quality control proteins (STOML2, PARL, YME1L1; SPY complex), with CLPB deficiency impeding SPY complex function by virtue of protein aggregation in the intermembrane space. We conclude that there is an interdependency of mitochondrial QC components at the intermembrane space/inner membrane interface, and perturbations to this network may underscore CLPB disease pathology.
HostingRepository	PRIDE
AnnounceDate	2024-01-18
AnnouncementXML	Submission_2024-01-17_18:51:58.943.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Megan Baker
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-18 01:03:13	ID requested
⏵ 1	2024-01-17 18:51:59	announced

10.1083/JCB.202305087;

submitter keyword: disaggregase, protein transport,mitochondria, protein quality control, mitochondrial disease

Diana Stojanovski
contact affiliation	Department of Biochemistry and Pharmacology and The Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, 3052, Australia
contact email	d.stojanovski@unimelb.edu.au
lab head
Megan Baker
contact affiliation	The University of Melbourne
contact email	meganb2@student.unimelb.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042313
     1. Label: PRIDE project
     2. Name: CLPB disaggregase dysfunction impacts the functional integrity of the proteolytic SPY complex