PXD002270-2

PXD002270 is an original dataset announced via ProteomeXchange.

Title	An impaired respiratory electron chain triggers retrograde response and de-ubiquitination of solute carrier amino acid transporters
Description	Hundreds of genes have been associated with respiratory chain disease so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, ��0 cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. Here, we integrated proteomic data sets including the post transcriptional modifications (PTM���s) phosphorylation and ubiquitination, with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK-. We applied a shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach to elucidate the consequences of the ��0 state. Pathway analysis revealed a non-uniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle and the pyruvate metabolism in ��0 cells. Surprisingly, some metabolites of the TCA cycle were dramatically reduced in ��0 cells, like citric acid (100-fold) and aconitic acid (6-fold), others instead increased, like succinic and fumaric acid (5-fold). Enzyme activities were xy. Exceptionally, the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus, was up-regulated in ��0 cells, like signalling by GPCR, EGFR, G12/13 alpha cAMP and RhoGTPase. We observed a striking de-ubiquitination of 80S ribosomal proteins (3-fold) and SLC amino acid transporters (7-fold) in ��0 cells, the later might cause the observed significant increase of amino acids levels in ��0 cells. We conclude that mtDNA depletion not only leads to an uneven down-regulation of mitochondrial energy pathways, but also to a strong retrograde response. The partly collapsed TCA cycle and de-ubiquitination of SLC transporters lead to an altered amino acid metabolism.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:33:27.270.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ina Gielisch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	ubiquitination signature dipeptidyl lysine; phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-05-31 23:50:25	ID requested
1	2022-02-22 04:04:06	announced
⏵ 2	2024-10-22 05:33:28	announced	2024-10-22: Updated project metadata.

Aretz I, Hardt C, Wittig I, Meierhofer D, An Impaired Respiratory Electron Chain Triggers Down-regulation of the Energy Metabolism and De-ubiquitination of Solute Carrier Amino Acid Transporters. Mol Cell Proteomics, 15(5):1526-38(2016) [pubmed]

10.1074/mcp.m115.053181;

curator keyword: Biomedical

submitter keyword: proteome profiling,ρ0 cells, metabolome profiling, mass spectrometry, ubiquitination, retrograde response, OXPHOS deficiency

David Meierhofer
contact affiliation	Max Planck Institute for Molecular Genetics, Ihnestrasse 63-72, 14195 Berlin, Germany
contact email	meierhof@molgen.mpg.de
lab head
Ina Gielisch
contact affiliation	MPIMG
contact email	gielisch@molgen.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002270
     1. Label: PRIDE project
     2. Name: An impaired respiratory electron chain triggers retrograde response and de-ubiquitination of solute carrier amino acid transporters