PXD019770-2

PXD019770 is an original dataset announced via ProteomeXchange.

Title	Acetyl-CoA flux maintains intracellular crosstalk and modulats engagement of the secretory pathway
Description	Nε-lysine acetylation has emerged as a central mechanism to maintain quality control and protein homeostasis within the Endoplasmic Reticulum (ER) and secretory pathway. The ER acetylation machinery includes AT-1/SLC33A1, a membrane transporter that translocates acetyl-CoA from the cytosol to the ER lumen, and ATase1 and ATase2, two ER membrane-bound acetyltransferases that acetylate ER cargo proteins. Dysfunctional AT-1, as caused by loss-of-function mutations or gene duplication events, results in neurodevelopmental or neurodegenerative disorders. Experiments in our lab have demonstrated that these human diseases can be effectively recapitulated in mouse models. In this thesis, we used two models of dysregulated acetyl-CoA flux: AT-1S113R/+, a model of AT-1 haploinsufficiency, and AT-1 sTg, a model of systemic overexpression of AT-1. First, we examined upstream processes of cytosol-to-ER acetyl-CoA flux by evaluating the cytosolic pool of acetyl-CoA. The aberrant AT-1 models demonstrated distinct metabolic reprogramming of lipid metabolism and mitochondria bioenergetics. Dysregulated acetyl-CoA flux resulted in global changes at the level of the proteome and the acetyl-proteome. Second, we examined the downstream consequences of cytosol-to-ER acetyl-CoA flux. Specifically, we investigated the engagement and functional organization of the secretory pathway and used N-glycoproteomics to determine the quality of secreted proteins. Aberrant AT-1 models demonstrated reorganization of the ER, Golgi, and ERGIC, as well as a delay in glycoproteins clearing the Golgi apparatus. Additionally, AT-1 sTg mice showed a marked delay in protein trafficking to the cell surface. The N-glycoproteome revealed significant alterations, highlighting changes in the quality of the secretome.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:28:47.751.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yusi Cui
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-15 02:49:47	ID requested
1	2021-09-09 04:07:42	announced
⏵ 2	2024-10-22 05:28:48	announced	2024-10-22: Updated project metadata.

10.1038/s41598-021-81447-6;

Dieterich IA, Cui Y, Braun MM, Lawton AJ, Robinson NH, Peotter JL, Yu Q, Casler JC, Glick BS, Audhya A, Denu JM, Li L, Puglielli L, Acetyl-CoA flux from the cytosol to the ER regulates engagement and quality of the secretory pathway. Sci Rep, 11(1):2013(2021) [pubmed]

submitter keyword: mouse, brain, glycoproteomics, LC-MS/MS

Lingjun Li
contact affiliation	School of Pharmacy, University of Wisconsin-Madison, Madison, WI, 53705, USA
contact email	lingjun.li@wisc.edu
lab head
Yusi Cui
contact affiliation	UW-Madison
contact email	cui42@wisc.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/2021/09/PXD019770

PRIDE project URI

• PRIDE
  1. PXD019770
     1. Label: PRIDE project
     2. Name: Acetyl-CoA flux maintains intracellular crosstalk and modulats engagement of the secretory pathway