PXD070711

PXD070711 is an original dataset announced via ProteomeXchange.

Title	Human Friedreich's Ataxia model proteomics
Description	Friedreich’s ataxia (FA) is a multisystem neurodegenerative disorder marked by early-onset sensory neuropathy and cardiomyopathy. However, the molecular determinants of tissue-specific vulnerability remain poorly understood. Here, we establish a human dual-cell model of FA by differentiating sensory neurons and cardiomyocytes from the same patients, enabling parallel molecular profiling of disease-relevant cell types. Proteomic analysis reveals distinct, cell-type-specific pathway disruptions in response to frataxin deficiency, reflecting divergent susceptibilities to mitochondrial dysfunction. Leveraging this platform, we investigate Miro1 Reducer 3 (MR3), a selective chemical probe targeting Miro1, a mitochondrial outer membrane GTPase implicated in redox regulation in FA. MR3 treatment modulates molecular signatures in a cell-type-dependent manner, enhancing pathways related to cardiac contractility in cardiomyocytes and synaptic function and cell-cell communication in sensory neurons. Mechanistically, MR3 reduces mitochondrial reactive oxygen species and restores membrane potential in FA sensory neurons via potential allosteric reshaping of Miro1 protein. To expand the chemical diversity of this scaffold, we conducted ligand-based virtual screening of over 3 billion compounds and identified multiple new Miro1 ligands with improved neuroprotective activity. These findings underscore the power of matched, patient-derived cell model in decoding cell-type-specific disease mechanisms and therapeutic responses, and highlight Miro1-targeted modulation as a promising therapeutic strategy in FA.
HostingRepository	PRIDE
AnnounceDate	2026-06-15
AnnouncementXML	Submission_2026-06-14_16:50:37.552.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD070711
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Sujyoti Chandra
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	S-carboxamidoethyl-L-cysteine; acetylated residue; monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2025-11-13 21:14:07	ID requested
⏵ 1	2026-06-14 16:50:38	announced

10.6019/PXD070711;

Chandra S, Kwak CS, Du Z, Barisano G, Nguyen KT, Vinogradov V, Wang X, Chemical modulation of Miro1 alleviates cell-type-specific vulnerabilities in Friedreich's ataxia. Cell Chem Biol, ():(2026) [pubmed]

10.1016/j.chembiol.2026.05.004;

submitter keyword: LFQ, Human Friedreich's Ataxia model proteomics

Xinan Wang
contact affiliation	Stanford university
contact email	xinnanw@stanford.edu
lab head
Sujyoti Chandra
contact affiliation	Instructor
contact email	sujyotic@stanford.edu
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/2026/06/PXD070711

PRIDE project URI

• PRIDE
  1. PXD070711
     1. Label: PRIDE project
     2. Name: Human Friedreich's Ataxia model proteomics