ArticleBMC biology2020
Multi-omics analysis delineates the distinct functions of sub-cellular acetyl-CoA pools in Toxoplasma gondii.
Article in BMC biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Systematic Review of Multi-Omics Approaches to Investigate Toxicological Effects in Macrophages.International journal of molecular sciences · 2020Pooled it
- Article
- Toxoplasma gondii SIR2A Promotes Tachyzoite Invasion via Lysine Deacetylase Activity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Inhibitors of the FASII Metabolic Pathway inMicroorganisms · 2026Review
- Transporters, an important but poorly studied area of Toxoplasma gondii.Parasites & vectors · 2026Review
- Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire.Proteomics · 2025Review
- Dissecting apicoplast functions through continuous cultivation of Toxoplasma gondii devoid of the organelle.Nature communications · 2025Article
- The apicoplast localized isocitrate dehydrogenase is needed forFrontiers in cellular and infection microbiology · 2025Article
- An endoplasmic reticulum localized acetyl-CoA transporter is required for efficient fatty acid synthesis inOpen biology · 2024Article
- N-acetylglucosamine supplementation fails to bypass the critical acetylation of glucosamine-6-phosphate required for Toxoplasma gondii replication and invasion.PLoS pathogens · 2024Article
- Proteomics Applications inPathogens (Basel, Switzerland) · 2023Review
- Article
- TgKDAC4: A Unique Deacetylase ofMicroorganisms · 2023Article
- The mitochondrion ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Development of a new quantification method of Sarcocystis cruzi through detection of the acetyl-CoA synthetase gene.The Journal of veterinary medical science · 2023Article
- Architecture, Chromatin and Gene Organization ofEpigenomes · 2022Article
- Toxoplasma metabolic flexibility in different growth conditions.Trends in parasitology · 2022Review
- Ceramide biosynthesis is critical for establishment of the intracellular niche of Toxoplasma gondii.Cell reports · 2022Article
- Toxoplasma gondii excretion of glycolytic products is associated with acidification of the parasitophorous vacuole during parasite egress.PLoS pathogens · 2022Article
- Preclinical characterization and target validation of the antimalarial pantothenamide MMV693183.Nature communications · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAcetyl-CoA is a key molecule in all organisms, implicated in several metabolic pathways as well as in transcriptional regulation and post-translational modification. The human pathogen Toxoplasma gondii possesses at least four enzymes which generate acetyl-CoA in the nucleo-cytosol (acetyl-CoA synthetase (ACS); ATP citrate lyase (ACL)), mitochondrion (branched-chain α-keto acid dehydrogenase-complex (BCKDH)) and apicoplast (pyruvate dehydrogenase complex (PDH)). Given the diverse functions of acetyl-CoA, we know very little about the role of sub-cellular acetyl-CoA pools in parasite physiology.
resultsTo assess the importance and functions of sub-cellular acetyl-CoA-pools, we measured the acetylome, transcriptome, proteome and metabolome of parasites lacking ACL/ACS or BCKDH. We demonstrate that ACL/ACS constitute a synthetic lethal pair. Loss of both enzymes causes a halt in fatty acid elongation, hypo-acetylation of nucleo-cytosolic and secretory proteins and broad changes in gene expression. In contrast, loss of BCKDH results in an altered TCA cycle, hypo-acetylation of mitochondrial proteins and few specific changes in gene expression. We provide evidence that changes in the acetylome, transcriptome and proteome of cells lacking BCKDH enable the metabolic adaptations and thus the survival of these parasites.
conclusionsUsing multi-omics and molecular tools, we obtain a global and integrative picture of the role of distinct acetyl-CoA pools in T. gondii physiology. Cytosolic acetyl-CoA is essential and is required for the synthesis of parasite-specific fatty acids. In contrast, loss of mitochondrial acetyl-CoA can be compensated for through metabolic adaptations implemented at the transcriptional, translational and post-translational level.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.