PXD016864

PXD016864 is an original dataset announced via ProteomeXchange.

Title	HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV
Description	Assembly factors play a critical role in the biogenesis of mitochondrial respiratory chain complexes I-IV where they assist in the membrane insertion of subunits, attachment of co-factors, and stabilization of assembly intermediates. The major fraction of complexes I, III and IV are present together in large molecular structures known as respiratory chain supercomplexes. A number of assembly factors have been proposed as required for supercomplex assembly, including the hypoxia inducible gene 1 domain family member HIGD2A. Using gene-edited human cell lines and extensive steady state, translation and affinity enrichment proteomics techniques we show that loss of HIGD2A leads to defects in the de novo biogenesis of mtDNA-encoded COX3, subsequent accumulation of complex IV intermediates and turnover of COX3 partner proteins. Deletion of HIGD2A also leads to defective complex IV activity. The impact of HIGD2A loss on complex IV was not altered by growth under hypoxic conditions, consistent with its role being in basal complex IV assembly. While in the absence of HIGD2A we show that mitochondria do contain an altered supercomplex assembly, we demonstrate it to harbor a crippled complex IV lacking COX3. Our results redefine HIGD2A as a classical assembly factor required for building the COX3 module of complex IV.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:02:29.337.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Stroud
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; 6x(13)C labeled residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos; Q Exactive; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-20 02:25:56	ID requested
1	2020-04-21 22:40:50	announced
2	2020-04-26 22:59:45	announced	2020-04-27: Updated publication reference for PubMed record(s): 32317297.
⏵ 3	2024-10-22 05:02:30	announced	2024-10-22: Updated project metadata.

10.1074/mcp.ra120.002076;

Hock DH, Reljic B, Ang CS, Muellner-Wong L, Mountford HS, Compton AG, Ryan MT, Thorburn DR, Stroud DA, HIGD2A is Required for Assembly of the COX3 Module of Human Mitochondrial Complex IV. Mol Cell Proteomics, 19(7):1145-1160(2020) [pubmed]

submitter keyword: assembly factor, Cytochrome c oxidase, hypoxia, respirasome,OXPHOS

David A. Stroud
contact affiliation	Department of Biochemistry and Molecular Biology Bio21 Molecular Science & Biotechnology Institute and The University of Melbourne 30 Flemington Road, Parkville VIC 3052 Australia
contact email	david.stroud@unimelb.edu.au
lab head
David Stroud
contact affiliation	The University of Melbourne
contact email	david.stroud@unimelb.edu.au
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/2020/04/PXD016864

PRIDE project URI

• PRIDE
  1. PXD016864
     1. Label: PRIDE project
     2. Name: HIGD2A is required for assembly of the COX3 module of human mitochondrial complex IV