PXD064926

PXD064926 is an original dataset announced via ProteomeXchange.

Title	Proteolytic Cleavage Activates the Mitochondrial Isoform of TOP3A
Description	The TOP3A gene encodes two isoforms, one targeted to the nucleus and one to mitochondria. Nuclear TOP3A functions as part of the BTRR complex to resolve double Holliday junctions during homologous recombination, while the mitochondrial isoform separates hemicatenated daughter mitochondrial DNA molecules following DNA replication. Here, we show that the mitochondrial isoform of TOP3A undergoes proteolytic cleavage by the mitochondrial processing peptidase (MPP), removing ~90 amino acids from the C-terminus. This cleavage enhances the enzyme’s biochemical properties, increasing single-stranded DNA binding and decatenation activity. Notably, all BTRR complex subunits except TOP3A are absent from mitochondria, suggesting that proteolytic processing enables TOP3A to function autonomously in mtDNA maintenance. We propose that this cleavage represents a post-import maturation step that tailors TOP3A to its mitochondrial context by uncoupling it from nuclear protein interactions and enhancing its catalytic efficiency.
HostingRepository	PRIDE
AnnounceDate	2025-10-01
AnnouncementXML	Submission_2025-10-01_04:43:55.851.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Proteomics Core Facility
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-06-12 04:17:33	ID requested
⏵ 1	2025-10-01 04:43:56	announced

Dataset with its publication pending

submitter keyword: TOP3A, mitochondria, mitochondrial processing peptidase (MMP), proteolytic cleavage product

Claes M. Gustafsson
contact affiliation	Department of Medical Biochemistry and Cell Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden
contact email	claes.gustafsson@medkem.gu.se
lab head
Proteomics Core Facility
contact affiliation	SAMBIO Core Facilities, Sahgrenska Academy, University of Gothenburg
contact email	gupcf@outlook.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/10/PXD064926

PRIDE project URI

• PRIDE
  1. PXD064926
     1. Label: PRIDE project
     2. Name: Proteolytic Cleavage Activates the Mitochondrial Isoform of TOP3A