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

ABSTRACT: 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.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: David Meierhofer  

PROVIDER: MSV000080873 | MassIVE | Sat Apr 01 04:09:00 BST 2017

SECONDARY ACCESSION(S): PXD002425

REPOSITORIES: MassIVE