MassIVE MSV000080873

Imported Reanalysis Dataset Public PXD002425

An impaired respiratory electron chain triggers down-regulation of the energy metabolism and de-ubiquitination of solute carrier amino acid transporters

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Description

We integrated metabolome and proteome profiles of the parental cell line 143B.TK- versus ?0, including PTM analyses such as phosphorylation and ubiquitination to characterize the impact of the absence of mtDNA for the entire cell. For quantitative proteome profiling, we used a shotgun LC-MS/MS approach including the classical SILAC labeling. For comprehensive metabolome profiling, we applied a targeted LC-MS approach, based on multiple reaction monitoring (MRM).

Our study revealed that mtDNA depletion leads to a non-uniform down-regulation of the mitochondrial energy metabolism in ?0 cells on the proteome level. Metabolites of the TCA cycle were highly dysregulated which in turn had an impact on the amino acid levels, which were up regulated. Perturbation of the mitochondrial energy metabolism could lead to an activation of the retrograde response, indicated by sets of up-regulated signaling pathways in ?0 cells, further supported by altered phosphorylation in signaling pathways and the cytoskeleton as well as de-ubiquitination of SLC transporters. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: �0 cells ; OXPHOS deficiency ; metabolome profiling ; proteome profiling ; mass spectrometry ; ubiquitination ; retrograde response

Contact

Principal Investigators:
(in alphabetical order) 		David Meierhofer, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-72, 14195 Berlin, Germany, N/A
Submitting User: ccms

Publications

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. 2016 May;15(5):1526-38. Epub 2016 Feb 6.

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