PXD013056-1

PXD013056 is an original dataset announced via ProteomeXchange.

Title	SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1
Description	Objective: 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.
HostingRepository	PRIDE
AnnounceDate	2019-04-18
AnnouncementXML	Submission_2019-04-18_02:52:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Johnson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-03-12 02:49:27	ID requested
⏵ 1	2019-04-18 02:53:08	announced
2	2019-05-21 05:34:32	announced	Updated publication reference for PubMed record(s): 31060926.
3	2024-10-22 04:11:53	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Brown adipose tissue

Thermogenesis

Thermoregulation

Mitochondria

Uncoupling protein 1

Sirtuin 3

Acetylation

Oxidative phosphorylation

Fatty acid oxidation

Acylcarnitines

Michael Downey
contact affiliation	University of Ottawa
contact email	mdowne2@uottawa.ca
lab head
Jeffrey Johnson
contact affiliation	UCSF
contact email	jeffrey.johnson@ucsf.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD013056
     1. Label: PRIDE project
     2. Name: SIRT3 controls brown fat thermogenesis by deacetylation regulation of pathways upstream of UCP1