PXD056813

PXD056813 is an original dataset announced via ProteomeXchange.

Title	Chemical proteomics reveal human off-targets of fluoroquinolone induced mitochondrial toxicity
Description	Fluoroquinolones (FQs) are an important class of potent broad-spectrum antibiotics. However, their general use is more and more limited by adverse side effects. While general mechanisms for the Fluoroquinolone-associated disability (FQAD) have been identified, the underlying molecular origins of toxicity remain elusive. In this study, focusing on the most commonly prescribed FQs Ciprofloxacin and Levofloxacin, whole proteome analyses revealed prominent mitochondrial dysfunction in human cells, specifically of the complexes I and IV of the electron transport chain. Furthermore, global untargeted chemo-proteomic methodologies such as photo-affinity profiling with FQ-derived probes, as well as derivatization-free thermal proteome profiling, were applied to elucidate human protein off-targets of FQs in living cells. Accordingly, the interactions of FQs with mitochondrial AIFM1 and IDH2 have been identified and biochemically validated for their contribution to mitochondrial dysfunction and adverse downstream effects, including impaired redox-homeostasis, elevated matrix metalloprotease activity and epigenetic modifications. This off-target discovery study provides unique insights into FQ toxicity enabling to utilize the identified molecular principles for the design of a safer FQ generation.
HostingRepository	PRIDE
AnnounceDate	2025-05-07
AnnouncementXML	Submission_2025-05-07_03:42:39.152.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Till Reinhardt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-10-15 03:54:46	ID requested
⏵ 1	2025-05-07 03:42:40	announced

10.1002/anie.202421424;

Reinhardt T, El Harraoui Y, Rothemann A, Jauch AT, M, ü, ller-Deubert S, K, ö, llen MF, Risch T, Jacobs LJ, M, ü, ller R, Traube FR, Docheva D, Zahler S, Riemer J, Bach NC, Sieber SA, Chemical Proteomics Reveals Human Off-Targets of Fluoroquinolone Induced Mitochondrial Toxicity. Angew Chem Int Ed Engl, 64(18):e202421424(2025) [pubmed]

submitter keyword: Human, Full Proteome, timsTOF Pro

Stephan Axel Sieber
contact affiliation	Center for Functional Protein Assemblies, TUM School of Natural Sciences, Technical University of Munich, Ernst-Otto-Fischer-Straße 8, 85748 Garching, Germany.
contact email	stephan.sieber@tum.de
lab head
Till Reinhardt
contact affiliation	Chair of Organic Chemistry II, Center for Functional Protein Assemblies, Department of Chemistry, Technical University of Munich
contact email	till.reinhardt@tum.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/2025/05/PXD056813

PRIDE project URI

• PRIDE
  1. PXD056813
     1. Label: PRIDE project
     2. Name: Chemical proteomics reveal human off-targets of fluoroquinolone induced mitochondrial toxicity