PXD001958

PXD001958 is an original dataset announced via ProteomeXchange.

Title	HEK293T Coa6 knockout mitochondria
Description	Biogenesis of complex IV of the mitochondrial respiratory chain requires assembly factors for subunit maturation, co-factor attachment and stabilization of intermediate assemblies. A pathogenic mutation in Coa6, leading to substitution of a conserved tryptophan to a cysteine residue, results in a loss of complex IV activity and cardiomyopathy. Here we demonstrate that the complex IV defect correlates with a severe loss in complex IV assembly in patient heart but not fibroblasts. Complete loss of Coa6 activity using gene-editing in HEK293T cells resulted in a profound growth defect due to complex IV deficiency, caused by impaired biogenesis of the copper-bound mtDNA encoded subunit COX2 and subsequent accumulation of complex IV assembly intermediates. We show that the pathogenic mutation in Coa6 does not affect its import into mitochondria but impairs its maturation and stability. Furthermore we find that Coa6 binds copper with a high affinity and also associates with mitochondrial copper chaperones, revealing that Coa6 is intricately involved in the copper-dependent biogenesis of COX2.
HostingRepository	PRIDE
AnnounceDate	2016-07-28
AnnouncementXML	Submission_2016-07-28_04:19:20.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	iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2015-03-24 06:36:13	ID requested
⏵ 1	2016-07-28 04:19:22	announced

Stroud DA, Maher MJ, Lindau C, V, ö, gtle FN, Frazier AE, Surgenor E, Mountford H, Singh AP, Bonas M, Oeljeklaus S, Warscheid B, Meisinger C, Thorburn DR, Ryan MT, COA6 is a mitochondrial complex IV assembly factor critical for biogenesis of mtDNA-encoded COX2. Hum Mol Genet, 24(19):5404-15(2015) [pubmed]

curator keyword: Biological

submitter keyword: Human, HEK293T, mitochondria

Michael Thomas Ryan
contact affiliation	Department of Biochemistry, Monash University
contact email	michael.ryan@monash.edu
lab head
David Stroud
contact affiliation	Monash University
contact email	d.stroud@monash.edu
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/2016/07/PXD001958

PRIDE project URI

• PRIDE
  1. PXD001958
     1. Label: PRIDE project
     2. Name: HEK293T Coa6 knockout mitochondria