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PXD022860

PXD022860 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomic analysis of whole brains from Ndufs4-/- mice treated with doxycycline
DescriptionMice with mitochondrial complex I deficiency (Ndufs4-/-) suffer from severe energy impairment primarily affecting the brain and die at P55. A small molecule screen developed by our lab using cells harboring human mitochondrial disease mutations identified antibiotics targeting mitochondrial translation as potent inhibitors of cell death under nutrient stress conditions. Doxycycline, which was identified amongst these antibiotics, was administered in the diet of Ndufs4-/- mice after weaning at P21. Mice fed with doxycycline showed improved motor function and significantly increased lifespan relative to untreated Ndufs4-/- mice. In order to investigate the molecular changes promoted by doxycycline in the brains of these mice, Ndufs4-/- doxycycline treated (DOX), Ndufs4-/- untreated (KO), and Ndufs4+/+ (WT) control mice were sacrificed at P55 and their brains harvested. Proteomic analysis revealed doxycycline treatment largely prevented the neuroimmune and inflammatory profile identified in the Ndufs4-/- mice. These findings implicate a potentially causality of these proteins in the neuronal cell death ultimately leading to the observed brain pathology.
HostingRepositoryPRIDE
AnnounceDate2021-09-09
AnnouncementXMLSubmission_2021-09-09_14:40:59.441.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmittermark Jedrychowski
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListTMT6plex-126 reporter+balance reagent acylated residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-12-01 23:43:02ID requested
12021-09-09 14:41:00announced
Publication List
Perry EA, Bennett CF, Luo C, Balsa E, Jedrychowski M, O'Malley KE, Latorre-Muro P, Ladley RP, Reda K, Wright PM, Gygi SP, Myers AG, Puigserver P, Tetracyclines promote survival and fitness in mitochondrial disease models. Nat Metab, 3(1):33-42(2021) [pubmed]
Keyword List
submitter keyword: Mitochondrial disease, Tetracycline, Mitochondrial translation, Mouse brain
Contact List
Pere Puigserver
contact affiliationDana Farber Cancer Institute Harvard Medical School Boston, Ma
contact emailPere_Puigserver@dfci.harvard.edu
lab head
mark Jedrychowski
contact affiliationHarvard Medical School
contact emailmark_jedrychowski@hms.harvard.edu
dataset submitter
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Dataset FTP location
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