PXD017000

PXD017000 is an original dataset announced via ProteomeXchange.

Title	Subcellular proteomics combined with bioenergetic phenotyping reveals protein biomarkers of respiratory insufficiency in the setting of compromised mitochondrial DNA repair.
Description	The mitochondrial mutator mouse is a well-established model of premature aging in which a progeroid phenotype is driven by the accumulation of somatic mtDNA mutations. Despite evidence of bioenergetic disruption within the cardiac mitochondria, there is little information about the underlying changes to the mitochondrial proteome. Herein, nLC-MS/MS was used to interrogate the mitochondria-enriched proteome of cardiac and skeletal muscle tissues of mutator mice and wild-type littermates. The mitochondrial proteome from heart tissue was then correlated with previously reported respiratory conductance data generated from the same mitochondrial samples to identify protein biomarkers of respiratory insufficiency. The majority of proteins that were found to be significantly downregulated in mutator mitochondria were subunits of respiratory complexes I and IV, including both nuclear and mitochondrial-encoded proteins. Interestingly, the mitochondrial-encoded complex V subunits, were unchanged or upregulated in mutator mitochondria suggesting a robustness to mtDNA mutation. Finally, the protein most strongly correlated with respiratory conductance in heart mitochondria from wild-type and mutator mice was the phosphatase PPM1K, which has been shown to have roles in branched chain amino acid metabolism and mitochondria permeability transition. These results suggest that mitochondrial mutator mice undergo a specific loss of mitochondrial complexes I and IV that limit their respiratory function independent of an upregulation of complex V. Additionally, the role of PPM1K in responding to mitochondrial stress warrants further exploration.
HostingRepository	jPOST
AnnounceDate	2021-01-08
AnnouncementXML	Submission_2022-09-18_03:17:03.661.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kelsey Fisher-Wellman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; TMT6plex reporter+balance reagent N-acylated residue; TMT6plex reporter+balance reagent acylated N-terminal
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-07 09:43:34	ID requested
1	2021-01-07 07:00:05	announced
2	2021-02-04 17:16:00	announced	2021-02-04: Updated FTP location.
⏵ 3	2022-09-18 03:17:04	announced	2022-09-18: Updated FTP location.

McLaughlin KL, Kew KA, McClung JM, Fisher-Wellman KH, Subcellular proteomics combined with bioenergetic phenotyping reveals protein biomarkers of respiratory insufficiency in the setting of proofreading-deficient mitochondrial polymerase. Sci Rep, 10(1):3603(2020) [pubmed]

submitter keyword: Mitochondrial proteome, mitochondrial DNA, DNA polymerase gamma, heart, skeletal muscle, TMT6plex

Kelsey Fisher-Wellman
lab head
Kelsey Fisher-Wellman
contact affiliation	East Carolina Diabetes and Obesity Institute
dataset submitter

jPOST dataset URI

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