PXD013736-2

PXD013736 is an original dataset announced via ProteomeXchange.

Title	Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk
Description	The acetyl-CoA transporter, AT-1 (also referred to as SLC33A1), is a key member of the endoplasmic reticulum (ER) acetylation machinery; it transports acetyl-CoA from the cytosol into the ER lumen where it serves as donor of the acetyl group for Nε-lysine acetylation 1,2. Dysfunctional ER acetylation, as caused by heterozygous or homozygous mutations as well as gene duplication events of AT-1/SLC33A1, has been linked to both developmental and age-associated human diseases 3-7. Mice with reduced or increased AT-1 expression mimic associated human diseases 8-10. In this study, we investigated the pervasive effects that dysregulated AT-1 has on intracellular acetyl-CoA homeostasis. Specifically, we used AT-1S113R/+ mice 8, a model of AT-1 haploinsufficiency, and AT-1 sTg mice 10, a model of AT-1 overexpression. We found that reduced AT-1 activity in AT-1S113R/+ mice led to increased availability of acetyl-CoA in the cytosol and spontaneous steatosis. Conversely, increased AT-1 activity decreased the availability of acetyl-CoA in the cytosol and made the animals resistant to diet-induced steatosis. Both models displayed significant metabolic adaptation involving different cellular organelles and compartments. Mechanistically, the metabolic adaptation was driven by changes in both protein levels (proteome) and stoichiometry of acetylation (acetylome) within fundamental pathways. Collectively, our results suggest that AT-1 acts as an important metabolic regulator that maintains acetyl-CoA homeostasis by promoting functional “cross-talk” between different intracellular organelles and compartments.
HostingRepository	PRIDE
AnnounceDate	2019-10-10
AnnouncementXML	Submission_2019-10-10_08:43:04.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	2019-05-07 03:42:09	ID requested
1	2019-08-05 03:16:32	announced
⏵ 2	2019-10-10 08:43:06	announced	2019-10-10: Updated project metadata.
3	2024-10-22 04:56:29	announced	2024-10-22: Updated project metadata.

Dieterich IA, Lawton AJ, Peng Y, Yu Q, Rhoads TW, Overmyer KA, Cui Y, Armstrong EA, Howell PR, Burhans MS, Li L, Denu JM, Coon JJ, Anderson RM, Puglielli L, Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk. Nat Commun, 10(1):3929(2019) [pubmed]

curator keyword: Biological

submitter keyword: Mouse, Liver, suborganelle, LC-MS/MS

Lingjun Li
contact affiliation	UW-Madison
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/2019/08/PXD013736

PRIDE project URI

• PRIDE
  1. PXD013736
     1. Label: PRIDE project
     2. Name: Acetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk