PXD042589

PXD042589 is an original dataset announced via ProteomeXchange.

Title	Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells
Description	Iron sulfur clusters (ISC) are essential cofactors that participate in electron transfer, environment sensing, and catalysis. Amongst the most ancient ISC containing proteins are the ferredoxin family of electron carriers. Humans have two ferredoxins, FDX1 and FDX2, localized to the mitochondria and important for ISC synthesis itself. We previously showed that hypoxia can bypass the requirement for some, but not all, components of the ISC biosynthetic pathway, but ferredoxins were not tested at that time. Here we report that FDX1 and its reductase FDXR, but not FDX2, are dispensable under ambient 1% O2 in cultured cells. We find that FDX1 is essential for production of the lipoic acid cofactor, which is synthesized by the ISC containing enzyme lipoyl synthase (LIAS). While hypoxia can rescue the growth phenotype of either FDX1 or LIAS knockout cells, lipoylation is not rescued, arguing against an alternative biosynthetic route or salvage pathway for lipoate in hypoxia. Our work identifies a role for FDX1/LIAS in lipoate synthesis and surprisingly reveals dispensability of lipoic acid altogether under low oxygen tensions in cell culture.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_06:49:25.516.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Xiaoyan Guo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-31 12:21:04	ID requested
1	2023-07-28 12:21:11	announced
⏵ 2	2023-11-14 06:49:25	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: metabolism, proteomics, TMT, FDX1, hypoxia, LIAS, mitochondria,lipoylation

Vamsi K.
contact affiliation	Howard Hughes Medical Institute and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Broad Institute, Cambridge, Massachusetts, United States of America; Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, United States of America.
contact email	vamsi@hms.harvard.edu
lab head
Xiaoyan Guo
contact affiliation	the Broad Institute
contact email	aguo@broadinstitute.org
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/2023/07/PXD042589

PRIDE project URI

• PRIDE
  1. PXD042589
     1. Label: PRIDE project
     2. Name: Lipoylation is dependent on the ferredoxin FDX1 and dispensable under hypoxia in human cells