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PXD039867 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleOxygen Toxicity Causes Cyclic Damage by Destabilizing Specific Fe-S Cluster-Containing Protein Complexes
DescriptionOxygen 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-05 10:25:37ID requested
12023-03-17 16:33:53announced
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]
Keyword List
submitter keyword: lung, hyperoxia, iron-sulfur cluster
Contact List
Isha Jain
contact affiliationGladstone Institutes
contact emailisha.jain@gladstone.ucsf.edu
lab head
contact affiliationGladstone Institutes
contact emailkirsten.chen@gladstone.ucsf.edu
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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