Dataset Information

Characterization of lysine acetylation in Toxoplasma gondii proteome lacking acetyl-CoA transporter 1 (AT1).

ABSTRACT: Acetyl-CoA participates in post-translational modification of proteins, central carbon and lipid metabolism in several cell compartments. In mammals, the acetyl-CoA transporter 1 (AT1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with dedicated acetyltransferases including Nat8. However, the implication of the ER acetyl-CoA pool in acetylation of ER-transiting proteins and their relevance throughout the parasites’ life cycle is unknown. Here, we evaluated the impact of blocking putative cytosolic acetyl-CoA import on acetylation of proteins through KO of the homologue of AT1 in the parasite Toxoplasma gondii.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human) Toxoplasma Gondii Rh

SUBMITTER: Yohann Couté

LAB HEAD: Yohann Couté

PROVIDER: PXD030932 | Pride | 2022-07-25

REPOSITORIES: Pride

ACCESS DATA

Publications

N-acetylation of secreted proteins in Apicomplexa is widespread and is independent of the ER acetyl-CoA transporter AT1.

Nyonda Mary Akinyi MA Boyer Jean-Baptiste JB Belmudes Lucid L Krishnan Aarti A Pino Paco P Couté Yohann Y Brochet Mathieu M Meinnel Thierry T Soldati-Favre Dominique D Giglione Carmela C

Journal of cell science 20220805 15

Acetyl-CoA participates in post-translational modification of proteins and in central carbon and lipid metabolism in several cell compartments. In mammals, acetyl-CoA transporter 1 (AT1, also known as SLC33A1) facilitates the flux of cytosolic acetyl-CoA into the endoplasmic reticulum (ER), enabling the acetylation of proteins of the secretory pathway, in concert with the activity of dedicated acetyltransferases such as NAT8. However, the involvement of the ER acetyl-CoA pool in acetylation of E ...[more]

PMID: 35621049

Similar Datasets

Project description:Cytosolic acetyl-coenzyme A is a precursor for many biotechnologically relevant compounds produced by Saccharomyces cerevisiae. In this yeast, cytosolic acetyl-CoA synthesis and growth strictly depend on expression of either the Acs1 or Acs2 isoenzyme of acetyl-CoA synthetase (ACS). Since hydrolysis of ATP to AMP and pyrophosphate in the ACS reaction constrains maximum yields of acetyl-CoA-derived products, this study explores replacement of ACS by two ATP-independent pathways for acetyl-CoA synthesis. After evaluating expression of different bacterial genes encoding acetylating acetaldehyde dehydrogenase (A-ALD) and pyruvate-formate lyase (PFL), acs1M-NM-^T acs2M-NM-^T S. cerevisiae strains were constructed in which A-ALD or PFL successfully replaced ACS. In A-ALD-dependent strains, aerobic growth rates of up to 0.27 h-1 were observed, while anaerobic growth rates of PFL-dependent S. cerevisiae (0.21 h-1) were stoichiometrically coupled to formate production. In glucose-limited chemostat cultures, intracellular metabolite analysis did not reveal major differences between A-ALD-dependent and reference strains. However, biomass yields on glucose of A-ALD- and PFL-dependent strains were lower than those of the reference strain. Transcriptome analysis suggested that reduced biomass yields were caused by acetaldehyde and formate in A-ALD- and PFL-dependent strains, respectively. Transcript profiles also indicated that a previously proposed role of Acs2 in histone acetylation is probably linked to cytosolic acetyl-CoA levels rather than to direct involvement of Acs2 in histone acetylation. While, for the first time, demonstrating that yeast ACS can be fully replaced by alternative reactions, this study demonstrates that further modifications are needed to achieve optimal in vivo efficiencies of the supply of acetyl-CoA as product precursor. To investigate the impact of introduced changes in native pathway of cytosolic acetyl-CoA formation in S. cerevisiae, a DNA microarray-based transcriptome analysis was performed on aerobic or anaerobic, glucose-limited chemostat cultures.

Dataset Information

Characterization of lysine acetylation in Toxoplasma gondii proteome lacking acetyl-CoA transporter 1 (AT1).

Publications

N-acetylation of secreted proteins in Apicomplexa is widespread and is independent of the ER acetyl-CoA transporter AT1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure