PXD023367

PXD023367 is an original dataset announced via ProteomeXchange.

Title	Loss of COX4i1 leads to combined respiratory chain deficiency and impaired mitochondrial protein synthesis
Description	The oxidative phosphorylation (OXPHOS) system localized in the inner mitochondrial membrane secures production of the majority of ATP in mammalian organisms. Individual OXPHOS complexes form supramolecular assemblies termed supercomplexes. The complexes are linked not only by their function but also by interdependence of individual complex biogenesis or maintenance. For instance, cytochrome c oxidase (cIV, COX) or cytochrome bc1 complex (cIII) deficiencies affect the level of fully assembled NADH dehydrogenase (cI) in monomeric as well as supercomplex forms. It was hypothesized that cI is affected at the level of enzyme assembly as well as at the level of cI stability and maintenance. However, the true nature of interdependency between cI and cIV is not fully understood yet. We used a HEK293 cellular model where the COX4 subunit was completely knocked out, serving as an ideal system to study interdependency of cI and cIV, as early phases of cIV assembly process are disrupted. Total absence of cIV was accompanied by profound deficiency of cI, documented by decrease in the levels of cI subunits and significantly reduced amount of assembled cI. Supercomplexes assembled from cI, cIII and cIV were missing in COX4 KO due to loss of cIV and decrease in cI amount. Pulse-chase metabolic labelling of mtDNA-encoded proteins uncovered a decrease in the translation of cIV and cI subunits. Moreover, partial impairment of mitochondrial protein synthesis correlated with decreased content of mitochondrial ribosomal proteins. In addition, complexome profiling revealed accumulation of cI assembly intermediates indicating that cI biogenesis, rather than stability, was the affected process. We propose, that impairment of mitochondrial protein synthesis caused by cIV deficiency represents one of the mechanisms which may couple biogenesis of cI and cIV.
HostingRepository	PRIDE
AnnounceDate	2021-02-18
AnnouncementXML	Submission_2021-02-18_13:29:52.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marek Vrbacky
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	methylthiolated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-01-04 02:24:06	ID requested
⏵ 1	2021-02-18 13:29:53	announced

Č, un, á, tov, á K, Reguera DP, Vrback, ý M, Fern, á, ndez-Vizarra E, Ding S, Fearnley IM, Zeviani M, Hou, š, t, ě, k J, Mr, á, č, ek T, Pecina P, Loss of COX4I1 Leads to Combined Respiratory Chain Deficiency and Impaired Mitochondrial Protein Synthesis. Cells, 10(2):(2021) [pubmed]

submitter keyword: mitochondria, OXPHOS, COX, COX4, knock-out, COX assembly, complex I, biogenesis interdependency, complexome profiling, mitochondrial protein synthesis

Tomas Mracek
contact affiliation	Laboratory of Bioenergetics, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic
contact email	tomas.mracek@fgu.cas.cz
lab head
Marek Vrbacky
contact affiliation	Czech Academy of Sciences
contact email	maralab@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD023367
     1. Label: PRIDE project
     2. Name: Loss of COX4i1 leads to combined respiratory chain deficiency and impaired mitochondrial protein synthesis