PXD068519-1

PXD068519 is an original dataset announced via ProteomeXchange.

Title	A single-amino-acid cleavage controls mitochondrial complexome stability
Description	Mitochondrial proteostasis depends on precise N-terminal processing of imported precursor proteins, and defects in this maturation step are implicated in severe human diseases, yet the functional impact in humans remain unclear. We show that the intermediate cleaving peptidase ICP55, that removes a single amino acid, acts as a key stabiliser of multimeric mitochondrial protein complexes. Using proteomics and complexome profiling, we identify over one hundred human ICP55 substrates and demonstrate that loss of ICP55 triggers proteome-wide destabilisation of protein assemblies, leading to the redistribution of their components into smaller subcomplexes. Our findings uncover a conserved, post-translational mechanism that safeguards mitochondrial proteostasis by regulating complex integrity through a single-amino-acid cleavage and reveal N-terminal proteoform control as an unexpected, novel layer of organellar homeostasis.
HostingRepository	PRIDE
AnnounceDate	2026-07-22
AnnouncementXML	Submission_2026-07-21_16:42:16.469.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marcin Luzarowski
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 00:06:34	ID requested
⏵ 1	2026-07-21 16:42:16	announced

Dataset with its publication pending

submitter keyword: complexome, N-terminome,ICP55, proteomics, co-fractionation, mass spectrometry

Marcin Luzarowski
contact affiliation	Core Facility for Mass Spectrometry and Proteomics, Center for Molecular Biology of Heidelberg University (ZMBH), DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany
contact email	m.luzarowski@zmbh.uni-heidelberg.de
lab head
Marcin Luzarowski
contact affiliation	University of Heidelberg
contact email	m.luzarowski@zmbh.uni-heidelberg.de
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/2026/07/PXD068519

PRIDE project URI

• PRIDE
  1. PXD068519
     1. Label: PRIDE project
     2. Name: A single-amino-acid cleavage controls mitochondrial complexome stability