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PXD028444-1

PXD028444 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleATF4-Mediate Changes in Protein Turnover During Age-Related Skeletal Muscle Atrophy
DescriptionAge-related skeletal muscle atrophy is a debilitating condition that has significant negative impacts on health and quality of life. Despite broad clinical impact, the molecular basis of age-related skeletal muscle atrophy is not well understood. Here, we determined protein turnover rates in skeletal muscle of 22-month-old control mice and 22-month-old muscle-specific ATF4 knockout (ATF4 mKO) mice, which are partially resistant to age-related muscle atrophy. All samples were analyzed by DDA TripleTOF 6600 mass spectrometer for downstream analysis of protein turnover. Quantitative MS1 peak areas were extracted from DDA raw files in the Skyline-Daily software platform. ProteinPilot search results were imported into the Skyline software to build a spectral library, followed by import of raw MS files for extraction of chromatographic peak areas. A custom skyline report containing all peptide and protein characteristics, annotations, and quantitative information including isotopologue peak areas was exported and used for downstream analysis and calculation of protein turnover rates in R using in-house R scripts (TurnoveR tool). Precursor-pool corrected protein turnover rates were calculated using the same approach employed in previous studies using the Topograph software platform. For calculation of protein abundance changes, DIA acquisitions from six samples (3 ATF4 KO and 3 WT samples) were quantitatively processed using Spectronaut v14. Analysis of protein turnover indicates that most proteins with altered turnover rates in ATF4 mKO muscles have decreased half-lives and are components of the mitochondrion. These proteins include subunits of the ATP Synthase (Atp5b, Atp5o), Ubiquinol-Cytochrome C Reductase (Uqcrc1, Uqcrh) and Cytochrome C Oxidase (Cox6b1) complexes, among others. These findings implicate increased rates of mitochondrial protein turnover as a mechanism that underlies, at least in part, the protection from age-induced muscle atrophy in ATF4 mKO mice.
HostingRepositoryMassIVE
AnnounceDate2021-09-10
AnnouncementXMLSubmission_2021-09-10_11:26:55.401.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNate
SpeciesList scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090;
ModificationList3x(2)H labeled L-leucine
InstrumentTripleTOF 6600
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-09-10 09:39:49ID requested
12021-09-10 11:26:55announced
Publication List
no publication
Keyword List
submitter keyword: aging, atrophy, skeletal muscle, sarcopenia, atf4, stable isotope labeling, protoeostasis, protein turnover
Contact List
Birgit Schilling
contact affiliationBuck Institute
contact emailbschilling@buckinstitute.org
lab head
Nate
contact affiliationThe Buck Institute for Research on Aging
contact emailnbasisty@buckinstitute.org
dataset submitter
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Dataset FTP location
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