Genome-Wide Identification and Characterization of Maize Long-Chain Acyl-CoA Synthetases and Their Expression Profiles in Different Tissues and in Response to Multiple Abiotic Stresses
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ABSTRACT:
SUBMITTER: Yan Z
PROVIDER: S-EPMC11354158 | biostudies-literature | 2024 Jul
REPOSITORIES: biostudies-literature
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Project description:Acyl-CoA synthetase enzymes are essential for de novo lipid synthesis, fatty acid catabolism, and remodeling of membranes. Activation of fatty acids requires a two-step reaction catalyzed by these enzymes. In the first step, an acyl-AMP intermediate is formed from ATP. AMP is then exchanged with CoA to produce the activated acyl-CoA. The release of AMP in this reaction defines the superfamily of AMP-forming enzymes. The length of the carbon chain of the fatty acid species defines the substrate specificity for the different acyl-CoA synthetases (ACS). On this basis, five sub-families of ACS have been characterized. The purpose of this review is to report on the large family of mammalian long-chain acyl-CoA synthetases (ACSL), which activate fatty acids with chain lengths of 12 to 20 carbon atoms. Five genes and several isoforms generated by alternative splicing have been identified and limited information is available on their localization. The structure of these membrane proteins has not been solved for the mammalian ACSLs but homology to a bacterial form, whose structure has been determined, points at specific structural features that are important for these enzymes across species. The bacterial form acts as a dimer and has a conserved short motif, called the fatty acid Gate domain, that seems to determine substrate specificity. We will discuss the characterization and identification of the different spliced isoforms, draw attention to the inconsistencies and errors in their annotations, and their cellular localizations. These membrane proteins act on membrane-bound substrates probably as homo- and as heterodimer complexes but have often been expressed as single recombinant isoforms, apparently purified as monomers and tested in Triton X-100 micelles. We will argue that such studies have failed to provide an accurate assessment of the activity and of the distinct function of these enzymes in mammalian cells.
| S-EPMC3377585 | biostudies-literature
Project description:Long-chain acyl-CoA synthetases (LACSs) catalyze fatty acids (FAs) to form fatty acyl-CoA thioesters, which play essential roles in FA and lipid metabolisms and cuticle wax biosynthesis. Although LACSs from Arabidopsis have been intensively studied, the characterization and function of LACSs from poplar are unexplored. Here, 10 poplar PtLACS genes were identified from the poplar genome and distributed to eight chromosomes. A phylogenetic tree indicated that PtLACSs are sorted into six clades. Collinearity analysis and duplication events demonstrated that PtLACSs expand through segmental replication events and experience purifying selective pressure during the evolutionary process. Expression patterns revealed that PtLACSs have divergent expression changes in response to abiotic stress. Interaction proteins and GO analysis could enhance the understanding of putative interactions among protein and gene regulatory networks related to FA and lipid metabolisms. Cluster networks and long-chain FA (LCFA) and very long-chain FA (VLCFA) content analysis revealed the possible regulatory mechanism in response to drought and salt stresses in poplar. The present study provides valuable information for the functional identification of PtLACSs in response to abiotic stress metabolism in poplar.
| S-EPMC9369374 | biostudies-literature
Project description:Each individual cell-type is defined by its distinct morphology, phenotype, molecular and lipidomic profile. The importance of maintaining cell-specific lipidomic profiles is exemplified by the numerous diseases, disorders, and dysfunctional outcomes that occur as a direct result of altered lipidome. Therefore, the mechanisms regulating cellular lipidome diversity play a role in maintaining essential biological functions. The brain is an organ particularly rich in phospholipids, the main constituents of cellular membranes. The phospholipid acyl-chain profile of membranes in the brain is rather diverse due in part to the high degree of cellular heterogeneity. These membranes and the acyl-chain composition of their phospholipids are highly regulated, but the mechanisms that confer this tight regulation are incompletely understood. A family of enzymes called acyl-CoA synthetases (ACSs) stands at a pinnacle step allowing influence over cellular acyl-chain selection and subsequent metabolic flux. ACSs perform the initial reaction for cellular fatty acid metabolism by ligating a Coenzyme A to a fatty acid which both traps a fatty acid within a cell and activates it for metabolism. The ACS family of enzymes is large and diverse consisting of 25-26 family members that are nonredundant, each with unique distribution across and within cell types, and differential fatty acid substrate preferences. Thus, ACSs confer a critical intracellular fatty acid selecting step in a cell-type dependent manner providing acyl-CoA moieties that serve as essential precursors for phospholipid synthesis and remodeling, and therefore serve as a key regulator of cellular membrane acyl-chain compositional diversity. Here we will discuss how the contribution of individual ACSs towards brain lipid metabolism has only just begun to be elucidated and discuss the possibilities for how ACSs may differentially regulate brain lipidomic diversity.
| S-EPMC8693597 | biostudies-literature
Project description:Thirteen homologous proteins comprise the long-chain acyl-CoA synthetase (ACSL), fatty acid transport protein (FATP), and bubblegum (ACSBG) subfamilies that activate long-chain and very-long-chain fatty acids to form acyl-CoAs. Gain- and loss-of-function studies show marked differences in the ability of these enzymes to channel fatty acids into different pathways of complex lipid synthesis. Further, the ability of the ACSLs and FATPs to enhance cellular FA uptake does not always require these proteins to be present on the plasma membrane; instead, FA uptake can be increased by enhancing its conversion to acyl-CoA and its metabolism in downstream pathways. Since altered fatty acid metabolism is a hallmark of numerous metabolic diseases and pathological conditions, the ACSL, FATP and ACSBG isoforms are likely to play important roles in disease etiology.
| S-EPMC2846691 | biostudies-literature
Project description:Peroxisomes carry out many essential lipid metabolic functions. Nearly all of these functions require that an acyl group-either a fatty acid or the acyl side chain of a steroid derivative-be thioesterified to coenzyme A (CoA) for subsequent reactions to proceed. This thioesterification, or "activation", reaction, catalyzed by enzymes belonging to the acyl-CoA synthetase family, is thus central to cellular lipid metabolism. However, despite our rather thorough understanding of peroxisomal metabolic pathways, surprisingly little is known about the specific peroxisomal acyl-CoA synthetases that participate in these pathways. Of the 26 acyl-CoA synthetases encoded by the human and mouse genomes, only a few have been reported to be peroxisomal, including ACSL4, SLC27A2, and SLC27A4. In this review, we briefly describe the primary peroxisomal lipid metabolic pathways in which fatty acyl-CoAs participate. Then, we examine the evidence for presence and functions of acyl-CoA synthetases in peroxisomes, much of which was obtained before the existence of multiple acyl-CoA synthetase isoenzymes was known. Finally, we discuss the role(s) of peroxisome-specific acyl-CoA synthetase isoforms in lipid metabolism.
| S-EPMC3382043 | biostudies-literature
Project description:IntroductionLong-chain acyl-CoA synthetases (ACSL) are implicated as regulators of oxidation and storage of fatty acids within skeletal muscle; however, to what extent diet and exercise alter skeletal muscle ACSL remains poorly understood.PurposeThis study aimed to determine the effects of diet and exercise training on skeletal muscle ACSL and to examine relationships between ACSL1 and ACSL6 and fat oxidation and fat storage, respectively.MethodsMale C57BL/6J mice consumed a 60% high-fat diet (HFD) for 12 wk to induce obesity compared with low-fat diet (LFD). At week 4, mice began aerobic exercise (EX-Tr) or remained sedentary (SED) for 8 wk. At week 12, the protein abundance of five known ACSL isoforms and mRNA expression for ACSL1 and ACSL6 were measured in gastrocnemius muscle, as was skeletal muscle lipid content. Fat oxidation was measured using metabolic cage indirect calorimetry at week 10.ResultsOf the five known ACSL isoforms, four were detected at the protein level. HFD resulted in greater, yet nonsignificant, ACSL1 protein abundance (+18%, P = 0.13 vs LFD), greater ACSL6 (+107%, P < 0.01 vs LFD), and no difference in ACSL4 or ACSL5. Exercise training resulted in greater ACSL6 protein abundance in LFD mice (P = 0.05 LFD EX-Tr vs SED), whereas ACSL4 was lower after exercise training compared with sedentary, regardless of diet. Under fasted conditions, skeletal muscle ACSL1 protein abundance was not related to measures of whole-body fat oxidation. Conversely, skeletal muscle ACSL6 protein abundance was positively correlated with intramyocellular lipid content (P < 0.01, r = 0.22).ConclusionWe present evidence that ACSL isoforms 1, 4, and 6 may undergo regulation by HFD and/or exercise training. We further conclude that increased skeletal muscle ACSL6 may facilitate increased intramyocellular fat storage during HFD-induced obesity.
| S-EPMC7024029 | biostudies-literature
Project description:The human AdipoR1 and AdipoR2 proteins, as well as their C. elegans homolog PAQR-2, protect against cell membrane rigidification by exogenous saturated fatty acids by regulating phospholipid composition. Here, we show that mutations in the C. elegans gene acs-13 help to suppress the phenotypes of paqr-2 mutant worms, including their characteristic membrane fluidity defects. acs-13 encodes a homolog of the human acyl-CoA synthetase ACSL1, and localizes to the mitochondrial membrane where it likely activates long chains fatty acids for import and degradation. Using siRNA combined with lipidomics and membrane fluidity assays (FRAP and Laurdan dye staining) we further show that the human ACSL1 potentiates lipotoxicity by the saturated fatty acid palmitate: silencing ACSL1 protects against the membrane rigidifying effects of palmitate and acts as a suppressor of AdipoR2 knockdown, thus echoing the C. elegans findings. We conclude that acs-13 mutations in C. elegans and ACSL1 knockdown in human cells prevent lipotoxicity by promoting increased levels of polyunsaturated fatty acid-containing phospholipids.
| S-EPMC6901333 | biostudies-literature
Project description:Transport of dietary lipids into small-intestinal epithelial cells is pathologically and nutritionally important. However, lipid uptake remains an almost unexplored research area. Although we know that long-chain bases (LCBs), constituents of sphingolipids, can enter into cells efficiently, the molecular mechanism of LCB uptake is completely unclear. Here, we found that the yeast acyl-CoA synthetases (ACSs) Faa1 and Faa4 are redundantly involved in LCB uptake. In addition to fatty acid-activating activity, transporter activity toward long-chain fatty acids (LCFAs) has been suggested for ACSs. Both LCB and LCFA transports were largely impaired in faa1Δ faa4Δ cells. Furthermore, LCB and LCFA uptakes were mutually competitive. However, the energy dependency was different for their transports. Sodium azide/2-deoxy-D-glucose treatment inhibited import of LCFA but not that of LCB. Furthermore, the ATP-AMP motif mutation FAA1 S271A largely impaired the metabolic activity and LCFA uptake, while leaving LCB import unaffected. These results indicate that only LCFA transport requires ATP. Since ACSs do not metabolize LCBs as substrates, Faa1 and Faa4 are likely directly involved in LCB transport. Furthermore, we revealed that ACSs are also involved in LCB transport in mammalian cells. Thus, our findings provide strong support for the hypothesis that ACSs directly transport LCFAs.
| S-EPMC4853782 | biostudies-literature
Project description:VQ motif-containing proteins play crucial roles in abiotic stress responses in plants. Recent studies have shown that some VQ proteins physically interact with WRKY transcription factors to activate downstream genes. In the present study, we identified and characterized genes encoding VQ motif-containing proteins using the most recent version of the maize genome sequence. In total, 61VQ genes were identified. In a cluster analysis, these genes clustered into nine groups together with their homologous genes in rice and Arabidopsis. Most of the VQ genes (57 out of 61 numbers) identified in maize were found to be single-copy genes. Analyses of RNA-seq data obtained using seedlings under long-term drought treatment showed that the expression levels of most ZmVQ genes (41 out of 61 members) changed during the drought stress response. Quantitative real-time PCR analyses showed that most of the ZmVQ genes were responsive to NaCl treatment. Also, approximately half of the ZmVQ genes were co-expressed with ZmWRKY genes. The identification of these VQ genes in the maize genome and knowledge of their expression profiles under drought and osmotic stresses will provide a solid foundation for exploring their specific functions in the abiotic stress responses of maize.
| S-EPMC4700186 | biostudies-literature
Project description:As crucial enzymes in the lipid metabolic network, long-chain acyl-CoA synthases (LACSs) are members of the acyl-activated enzyme superfamily and play a crucial role in epidermal wax synthesis, plant lipid anabolic metabolism, and stress tolerance. In this study, 11 pecan LACS genes were identified and categorized into five groups and located on nine chromosomes. The significant degree of conservation in the AtLACS and CiLACS protein sequences was demonstrated by multiple sequence alignment and conserved motif analysis. Cis-acting element analysis identified numerous stress-responsive and hormone-inducible elements in the promoter regions of CiLACS genes. The expression levels of CiLACS9 and CiLACS9-1 were considerably up-regulated under salt and drought stress, according to the qRT-RCR study. Treatment with ABA also led to increased expression levels of CiLACS1, CiLACS1-1, CiLACS2, and CiLACS9-1. Notably, CiLACS4, CiLACS4-1, CiLACS9, and CiLACS9-1 exhibited peak expression levels at 135 days after anthesis and are likely to have been crucial in the accumulation of seed kernel oil. Moreover, the CiLACS9 gene was shown to be located in the cytoplasm. These findings offer a theoretical framework for clarifying the roles of LACS genes in the processes of pecan kernel oil synthesis and response to abiotic stressors.
| S-EPMC10380667 | biostudies-literature