PXD020128-2

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	2020-07-27
AnnouncementXML	Submission_2020-09-11_03:41:36.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.

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

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

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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