PXD033884

PXD033884 is an original dataset announced via ProteomeXchange.

Title	Fitm2 is required for ER homeostasis and normal function of murine liver
Description	The ER-resident prote in fat-inducing transcript 2 (FIT2) catalyzes acyl-CoA cleavage in vitro, and in cells is required for endoplasmic reticulum (ER)homeostasis and normal lipid storage. The gene encoding FIT2 is essential for viability of mice and worms. Whether FIT2 acts as anacyl-CoA diphosphatase in vivo and how this activity affects liver, where the protein was discovered,is unknown. Here, we report that hepatocyte-specific Fitm2 knockout (FIT2-LKO) mice exhibited elevated acyl-CoA levels, ER stress, and signs of liver injury. FIT2-LKO mice had increased triglyceride (TG) content in liver when fed a chow diet, compared with control littermates due in part to impaired secretion of TG-rich lipoproteins and reduced capacity for fatty acid oxidation. Challenging FIT2-LKO mice with a high-fat diet to increase FIT2 acyl-CoA substrates worsened hepatic ER stress and liver injury, yet unexpectedly reversed the steatosis phenotype, similar to what is observed in FIT2-deficient cells loaded with fatty acids. Our findings show that FIT2 acts as anacyl-CoA diphosphatase in vivo and is crucial for normal hepatocyte function and ER homeostasis in murine liver
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:45:52.618.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Zon Weng Lai
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-13 06:48:55	ID requested
1	2023-05-10 09:09:20	announced
⏵ 2	2023-11-14 08:45:53	announced	2023-11-14: Updated project metadata.

Bond LM, Ibrahim A, Lai ZW, Walzem RL, Bronson RT, Ilkayeva OR, Walther TC, Farese RV, murine liver. J Biol Chem, 299(3):103022(2023) [pubmed]

submitter keyword: lipid metabolism, acyl-CoA, endoplasmic reticulum, liver,FITM2

Tobias Walther
contact affiliation	Harvard T.H. Chan School of Public Health Harvard Medical School
contact email	twalther@hsph.harvard.edu
lab head
Zon Weng Lai
contact affiliation	Harvard T. H. Chan School of Public Health
contact email	zlai@hsph.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/05/PXD033884

PRIDE project URI

• PRIDE
  1. PXD033884
     1. Label: PRIDE project
     2. Name: Fitm2 is required for ER homeostasis and normal function of murine liver