Synergistic roles of acyl-CoA binding protein (ACBP1) and sterol carrier protein 2 (SCP2) in<i>Toxoplasma</i>lipid metabolism

Fu, Yong; Cui, Xia; Liu, Jing; Zhang, Xiao; Zhang, Heng; Yang, Chenxue; Li, Qun

doi:10.1111/cmi.12970

Cited by 12 publications

(7 citation statements)

References 36 publications

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“…In addition, eight malonylated proteins in T. gondii belonged to the fatty acid biosynthesis ( Figure 4B). These are involved in the growth, development, and reproduction of T. gondii (Fu et al, 2019). Malonyl-CoA can serve as a substrate of fatty acid synthesis and as an inhibitor of fatty acid oxidation (Foster, 2012).…”

Section: Advanced Functional Enrichment Of Malonylated Proteinsmentioning

confidence: 99%

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Nie

Liang

et al. 2020

Front. Microbiol.

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Lysine malonylation (Kmal) is a new post-translational modification (PTM), which has been reported in several prokaryotic and eukaryotic species. Although Kmal can regulate many and diverse biological processes in various organisms, knowledge about this important PTM in the apicomplexan parasite Toxoplasma gondii is limited. In this study, we performed the first global profiling of malonylated proteins in T. gondii tachyzoites using affinity enrichment and Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Three experiments performed in tandem revealed 294, 345, 352 Kmal sites on 203, 236, 230 malonylated proteins, respectively. Computational analysis showed the identified malonylated proteins to be localized in various subcellular compartments and involved in many cellular functions, particularly mitochondrial function. Additionally, one conserved Kmal motif with a strong bias for cysteine was detected. Taken together, these findings provide the first report of Kmal profile in T. gondii and should be an important resource for studying the physiological roles of Kmal in this parasite.

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Section: Advanced Functional Enrichment Of Malonylated Proteinsmentioning

confidence: 99%

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Nie

Liang

et al. 2020

Front. Microbiol.

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“…TAG is formed by redundant non-esterified free fatty acids, which are cytotoxic at high concentration, in a selfprotective manner [52]. In addition, our laboratory has previously shown that disruption of ACBP alone in Toxoplasma did not affect the growth ability and intracellular replication, which is the same as NcACBP knockout phenotypes in vitro [24]. However, TgACBP disruption did not affect the virulence to mice while NcACBP knockout enhanced the pathogenicity to mice.…”

Section: Discussionmentioning

confidence: 91%

“…In Cryptosporidium parvum, ACBP is presumed to play roles in lipid metabolism and trafficking in parasitophorous vacuoles (PV) [23]. Recently, our laboratory showed that acyl-CoA binding protein and sterol carrier protein 2 in Toxoplasma cooperate in lipid metabolism [24]. As Neospora structurally and morphologically resembles Toxoplasma, we hypothesized that Neospora may depend on the same fatty acid metabolic pathways in which acyl-CoA binding protein determines the metabolic fate of fatty acids.…”

Section: Open Accessmentioning

confidence: 99%

Functional characterization of acyl-CoA binding protein in Neospora caninum

Zhou

Zhang

et al. 2020

Parasites Vectors

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Background: Lipid metabolism is pivotal for the growth of apicomplexan parasites. Lipid synthesis requires bulk carbon skeleton acyl-CoAs, the transport of which depends on the acyl-CoA binding protein (ACBP). In Neospora caninum, the causative agent of neosporosis, the FASII pathway is required for growth and pathogenicity. However, little is known about the fatty acid transport mechanism in N. caninum. Methods:We have identified a cytosolic acyl-CoA binding protein, with highly conserved amino acid residues and a typical acyl-CoA binding domain in N. caninum. The recombinant NcACBP protein was expressed to verify the binding activities of NcACBP in vitro, and the heterologous expression of NcACBP in Δacbp yeast in vivo. Lipid extraction from ΔNcACBP or the wild-type of N. caninum was analyzed by GC-MS or TLC. Furthermore, transcriptome analysis was performed to compare the gene expression in different strains.Results: The NcACBP recombinant protein was able to specifically bind acyl-CoA esters in vitro. A yeast complementation assay showed that heterologous expression of NcACBP rescued the phenotypic defects in Δacbp yeast, indicating of the binding activity of NcACBP in vivo. The disruption of NcACBP did not perturb the parasite's growth but enhanced its pathogenicity in mice. The lipidomic analysis showed that disruption of NcACBP caused no obvious changes in the overall abundance and turnover of fatty acids while knockout resulted in the accumulation of triacylglycerol. Transcriptional analysis of ACBP-deficient parasites revealed differentially expressed genes involved in a wide range of biological processes such as lipid metabolism, posttranslational modification, and membrane biogenesis. Conclusions:Our study demonstrated that genetic ablation of NcACBP did not impair the survival and growth phenotype of N. caninum but enhanced its pathogenicity in mice. This deletion did not affect the overall fatty acid composition but modified the abundance of TAG. The loss of NcACBP resulted in global changes in the expression of multiple genes. This study provides a foundation for elucidating the molecular mechanism of lipid metabolism in N. caninum.

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“…Toxoplasma also has 6 ATP-binding cassette G family transporter (ABCG), which localizes differentially within the parasite and are shown to be involved in phospholipid and cholesterol import/efflux [ 72 ]. Not only can these parasites scavenge FA, but they can also recruit whole phospholipids [ 42 , 73 ] and neutral lipid stores directly from the host [ 47 ]. Phospholipid synthesis is facilitated by the scavenging of precursors such as serine, ethanolamine, and choline from the host environment.…”

Section: Lipid Scavenging Mechanismsmentioning

confidence: 99%

“…The genome of Toxoplasma has no FABP but encodes for 2 ACBPs and are involved in lipid signaling and metabolism. In the absence of the cytosol Tg ACBP1, there is a decreased abundance of C18:1, which is predominantly scavenged from the host [ 73 ]. The mitochondrial Tg ACBP2 plays a key role in cardiolipin metabolism and is critical of the growth and virulence of type II parasites [ 77 ].…”

Section: Lipid Scavenging Mechanismsmentioning

confidence: 99%

The flexibility of Apicomplexa parasites in lipid metabolism

et al. 2022

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Apicomplexa are obligate intracellular parasites responsible for major human infectious diseases such as toxoplasmosis and malaria, which pose social and economic burdens around the world. To survive and propagate, these parasites need to acquire a significant number of essential biomolecules from their hosts. Among these biomolecules, lipids are a key metabolite required for parasite membrane biogenesis, signaling events, and energy storage. Parasites can either scavenge lipids from their host or synthesize them de novo in a relict plastid, the apicoplast. During their complex life cycle (sexual/asexual/dormant), Apicomplexa infect a large variety of cells and their metabolic flexibility allows them to adapt to different host environments such as low/high fat content or low/high sugar levels. In this review, we discuss the role of lipids in Apicomplexa parasites and summarize recent findings on the metabolic mechanisms in host nutrient adaptation.

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Synergistic roles of acyl-CoA binding protein (ACBP1) and sterol carrier protein 2 (SCP2) inToxoplasmalipid metabolism

Cited by 12 publications

References 36 publications

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Global Proteomic Analysis of Lysine Malonylation in Toxoplasma gondii

Functional characterization of acyl-CoA binding protein in Neospora caninum

The flexibility of Apicomplexa parasites in lipid metabolism

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