PXD029270-1

PXD029270 is an original dataset announced via ProteomeXchange.

Title	Cysteine 253 of UCP1 regulates energy expenditure and adipose tissue inflammation
Description	Uncoupling protein 1 (UCP1) is thought to be a major regulator of whole-body energy expenditure and metabolic homeostasis. However, the widely employed UCP1 loss of function model has recently been shown to have destructive effects on the entire electron transport chain of thermogenic fat. As such, the role of UCP1 in metabolic regulation in vivo remains unclear. We recently identified cysteine-253 as an allosteric site on UCP1 that elevates protein activity upon covalent modification. Here we examine the physiological importance of this site through the generation of a UCP1 cysteine-253 null mouse (UCP1 C253A), the first genetic model for selective disruption of UCP1 in vivo. UCP1 C253A mice exhibit significantly compromised thermogenic responses but display no measurable effect on fat accumulation in an obesogenic environment. Unexpectedly, instead we find that lack of cysteine-253 results in substantial immune cell infiltration and inflammatory pathology in adipose tissues of male, but not female mice. Together, our results establish the UCP1 cysteine-253 activation site as a regulator of acute thermogenesis and sex-dependent adipose tissue inflammation.
HostingRepository	PRIDE
AnnounceDate	2021-12-15
AnnouncementXML	Submission_2021-12-15_03:06:33.374.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Haopeng Xiao
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Eclipse; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-21 05:53:03	ID requested
⏵ 1	2021-12-15 03:06:33	announced

Dataset with its publication pending

submitter keyword: Thermogenesis, UCP1, inflammation, adipose, sex-dependent

Edward Chouchani
contact affiliation	1 Department of Cancer Biology, Dana–Farber Cancer Institute, Boston, MA, USA. 2 Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
contact email	EdwardT_Chouchani@DFCI.HARVARD.EDU
lab head
Haopeng Xiao
contact affiliation	Dana-Farber Cancer Institute/Harvard Medical School
contact email	haopeng_xiao@dfci.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029270
     1. Label: PRIDE project
     2. Name: Cysteine 253 of UCP1 regulates energy expenditure and adipose tissue inflammation