PXD039867

PXD039867 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	Oxygen Toxicity Causes Cyclic Damage by Destabilizing Specific Fe-S Cluster-Containing Protein Complexes
Description	Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.
HostingRepository	MassIVE
AnnounceDate	2023-03-17
AnnouncementXML	Submission_2023-03-17_16:33:53.088.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	kirsten.chen
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList	Oxidation
Instrument	Orbitrap Fusion Lumos

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-05 10:25:37	ID requested
⏵ 1	2023-03-17 16:33:53	announced

Publication List

Baik AH, Haribowo AG, Chen X, Queliconi BB, Barrios AM, Garg A, Maishan M, Campos AR, Matthay MA, Jain IH, Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes. Mol Cell, 83(6):942-960.e9(2023) [pubmed]

Baik AH, Haribowo AG, Chen X, Queliconi BB, Barrios AM, Garg A, Maishan M, Campos AR, Matthay MA, Jain IH, Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes. Mol Cell, 83(6):942-960.e9(2023) [pubmed]

Keyword List

submitter keyword: lung, hyperoxia, iron-sulfur cluster

submitter keyword: lung, hyperoxia, iron-sulfur cluster

Contact List

Isha Jain
contact affiliation	Gladstone Institutes
contact email	isha.jain@gladstone.ucsf.edu
lab head
kirsten.chen
contact affiliation	Gladstone Institutes
contact email	kirsten.chen@gladstone.ucsf.edu
dataset submitter

Full Dataset Link List

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MassIVE dataset URI

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://massive.ucsd.edu/MSV000091206/