PXD072438

PXD072438 is an original dataset announced via ProteomeXchange.

Title	Crosslinker Nanocarriers-based Intratumoral Delivery for Protein Complex Mapping in Mitochondria of Live Tumor-Bearing Mice
Description	Mitochondria, the powerhouses of the cell, are central to tumor initiation and growth, yet their protein interactions in living tumors remain poorly understood. Although crosslinking mass spectrometry (XL-MS) has provided valuable insights in cultured cells and isolated tissues, in vivo application is limited by poor crosslinker delivery. Here, we present an approach that uses intratumoral injection of crosslinker-loaded nanoparticles in xenografted mice to enable in vivo DSS crosslinking of tumor mitochondria, thereby facilitating XL-MS–based analysis of mitochondrial protein complexes. We identified 2,368 crosslinked peptides from 654 mitochondrial proteins, covering 58% of the human mitochondrial proteome. Among these, 553 crosslinked peptides were mapped to proteins involved in thermogenesis, ribosome function, and branched-chain amino acid degradation—metabolic pathways closely linked to tumor progression. Structural concordance was high (91%) with PDB and AlphaFold models, and complementary conformational insights were obtained, including previously missing data on the DAPIT subunit of ATP synthase, thus complementing cryo-electron microscopy (cryo-EM) structures. We further mapped 217 mitochondrial PPIs, including 146 not annotated in STRING, highlighting the influence of the tumor microenvironment on protein interactions in vivo and providing valuable insights into tumor biology.
HostingRepository	iProX
AnnounceDate	2025-12-26
AnnouncementXML	Submission_2026-03-27_02:00:21.149.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenxin Fu
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-26 01:09:42	ID requested
⏵ 1	2026-03-27 02:00:21	announced

Dataset with its publication pending

submitter keyword: PLGA nanoparticles, vivo crosslinking

Lihua Zhang
contact affiliation	Dalian Institute of Chemical Physics, Chinese Academy of Sciences
contact email	lihuazhang@dicp.ac.cn
lab head
Wenxin Fu
contact affiliation	Dalian Institute of Chemical Physics, Chinese Academy of Sciences
contact email	fuwenxin@dicp.ac.cn
dataset submitter

iProX dataset URI