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PXD013736 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAcetyl-CoA flux regulates the proteome and acetyl-proteome to maintain intracellular metabolic crosstalk
DescriptionThe 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.
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterYusi Cui
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListmonohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Fusion Lumos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-05-07 03:42:09ID requested
12019-08-05 03:16:32announced
22019-10-10 08:43:06announced2019-10-10: Updated project metadata.
Publication List
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]
Keyword List
curator keyword: Biological
submitter keyword: Mouse, Liver, suborganelle, LC-MS/MS
Contact List
Lingjun Li
contact affiliationUW-Madison
contact emaillingjun.li@wisc.edu
lab head
Yusi Cui
contact affiliationUW-Madison
contact emailcui42@wisc.edu
dataset submitter
Full Dataset Link List
Dataset FTP location
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