PXD020128-3

PXD020128 is an original dataset announced via ProteomeXchange.

Title	ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex
Description	2-oxoglutarate (2-OG or α-ketoglutarate) relates mitochondrial metabolism to cell function by modulating the activity of 2-OG dependent dioxygenases involved in the hypoxia response and DNA/histone modifications. However, metabolic pathways that regulate these oxygen and 2-OG sensitive enzymes remain poorly understood. Here, using CRISPR Cas9 genome-wide utagenesis to screen for genetic determinants of 2-OG levels, we uncover a redox sensitive mitochondrial lipoylation pathway, dependent on the mitochondrial hydrolase ABHD11, that signals changes in mitochondrial 2-OG metabolism to 2-OG dependent dioxygenase function. ABHD11 loss or inhibition drives a rapid increase in 2-OG levels by impairing lipoylation of the 2-OG dehydrogenase complex (OGDHc) – the rate limiting step for mitochondrial 2-OG metabolism. Rather than facilitating lipoate conjugation, ABHD11 associates with the OGDHc and maintains catalytic activity of lipoyl domain by preventing the formation of lipoyl adducts, highlighting ABHD11 as a regulator of functional lipoylation and 2-OG metabolism.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:09:55.779.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jack Houghton
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	N6-lipoyl-L-lysine
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-30 18:21:09	ID requested
1	2020-07-27 02:22:57	announced
2	2020-09-11 03:41:37	announced	2020-09-11: Updated publication reference for PubMed record(s): 32792488.
⏵ 3	2024-10-22 05:10:01	announced	2024-10-22: Updated project metadata.

10.1038/s41467-020-17862-6;

Bailey PSJ, Ortmann BM, Martinelli AW, Houghton JW, Costa ASH, Burr SP, Antrobus R, Frezza C, Nathan JA, ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex. Nat Commun, 11(1):4046(2020) [pubmed]

submitter keyword: α-ketoglutarate, lipid peroxidation, 2-oxoglutarate dehydrogenase complex, lipoic acid, Hypoxia Inducible Factor,2-oxoglutarate, ABHD11, lipoylation, α-ketoglutarate dehydrogenase complex

James A Nathan
contact affiliation	Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre Cambridge Biomedical Campus, University of Cambridge, Cambridge, CB2 0AW, UK.
contact email	jan33@cam.ac.uk
lab head
Jack Houghton
contact affiliation	University of Cambridge
contact email	jwh65@cam.ac.uk
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/2020/07/PXD020128

PRIDE project URI

• PRIDE
  1. PXD020128
     1. Label: PRIDE project
     2. Name: ABHD11 maintains 2-oxoglutarate metabolism by preserving functional lipoylation of the 2-oxoglutarate dehydrogenase complex