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PXD013056

PXD013056 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1 

DescriptionObjective: Brown adipose tissue (BAT) is important for thermoregulation in many mammals. Uncoupling protein 1 (UCP1) is the critical regulator of thermogenesis in BAT. Here we aimed to investigate the deacetylation control of BAT and to investigate a possible functional connection between UCP1 and sirtuin 3 (SIRT3), the master mitochondrial deacetylase. 
 Methods: We carried out physiological, molecular and proteomic analyses of BAT from wild-type and Sirt3KO mice when BAT is activated. Mice were either cold exposed for 2 days or were injected with the β3-adrenergic agonist, CL316,243 (1mg/kg; i.p.). Mutagenesis studies were conducted in a cellular model to assess the impact of acetyaltion lysine sites on UCP1 function. Cardiac punctures were collected for Proteomic analysis of Acylcarnitines. Isolated mitochondria were used for functional analysis of OXPHOS. 
 Results: Our findings showed that SIRT3 absence in mice resulted in impaired BAT lipid use, whole body thermoregulation, and respiration in BAT mitochondria, without affecting UCP1 expression. Acetylome profiling of BAT mitochondria revealed that SIRT3 regulates acetylation status of many BAT mitochondrial proteins including UCP1 and crucial upstream proteins. Mutagenesis work in cells suggested that UCP1 activity was independent of direct SIRT3-regulated lysine acetylation. However, SIRT3 impacted BAT mitochondrial activities of acylcarnitine metabolism and specific electron transport chain complexes, CI and CII. 

HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:11:51.697.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterJeffrey Johnson
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue
InstrumentOrbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-03-12 02:49:27ID requested
12019-04-18 02:53:08announced
22019-05-21 05:34:32announcedUpdated publication reference for PubMed record(s): 31060926.
32024-10-22 04:11:53announced2024-10-22: Updated project metadata.
Publication List
Sebaa R, Johnson J, Pileggi C, Norgren M, Xuan J, Sai Y, Tong Q, Krystkowiak I, Bondy-Chorney E, Davey NE, Krogan N, Downey M, Harper ME, SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1. Mol Metab, 25():35-49(2019) [pubmed]
10.1016/j.molmet.2019.04.008;
Keyword List
submitter keyword: Brown adipose tissue
Thermogenesis
Thermoregulation
Mitochondria
Uncoupling protein 1
Sirtuin 3
Acetylation
Oxidative phosphorylation
Fatty acid oxidation
Acylcarnitines 

Contact List
Michael Downey
contact affiliationUniversity of Ottawa
contact emailmdowne2@uottawa.ca
lab head
Jeffrey Johnson
contact affiliationUCSF
contact emailjeffrey.johnson@ucsf.edu
dataset submitter
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Dataset FTP location
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