scholarly journals Peroxisomal ATP uptake is managed by the ABC transporters and two adenine nucleotide transporters

2021 ◽  
Author(s):  
Carlo W.T. van Roermund ◽  
L. IJlst ◽  
Nicole Linka ◽  
R.J.A. Wanders ◽  
Hans R. Waterham
Keyword(s):  
Adenine Nucleotide ◽  
Beta Oxidation ◽  
Peroxisomal Membrane ◽  
Yeast Saccharomyces Cerevisiae ◽  
Targeted Deletion ◽  
Transporter Protein ◽  
Metabolic Functions ◽  
Atp Levels ◽  
Dual Localization ◽  
Fatty Acid Beta Oxidation

Peroxisomes are essential organelles involved in various metabolic processes, including fatty acid beta-oxidation. Their metabolic functions require a controlled exchange of metabolites and co-factors, including ATP across the peroxisomal membrane. We investigated which proteins are involved in the peroxisomal uptake of ATP in the yeast Saccharomyces cerevisiae. Using wild-type and targeted deletion strains, we measured ATP-dependent peroxisomal octanoate beta-oxidation, intra-peroxisomal ATP levels employing peroxisome-targeted ATP-sensing reporter proteins, and ATP uptake in proteoliposomes prepared from purified peroxisomes. We show that intra-peroxisomal ATP levels are maintained by different peroxisomal membrane proteins each with different modes of action: (1) the previously reported Ant1p protein, which catalyzes ATP/AMP exchange (2) the ABC transporter protein complex Pxa1p/Pxa2p, which mediates both acyl-CoA and ATP uptake; and; (3) the mitochondrial Aac2p protein, which catalyzes ATP/ADP exchange and was shown to have a dual localization in both mitochondria and peroxisomes. Our results provide compelling evidence for an ingenious complementary system for the uptake of ATP in peroxisomes.

scholarly journals Exploring the metabolic landscape of pancreatic ductal adenocarcinoma cells using genome-scale metabolic modeling

2021 ◽  
Author(s):  
Mohammad Mazharul Islam ◽  
Andrea Goertzen ◽  
Pankaj Kumar Singh ◽  
Rajib Saha
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapy Response ◽  
Metabolic Model ◽  
Ductal Adenocarcinoma ◽  
Patient Specific ◽  
Beta Oxidation ◽  
Metabolic Functions ◽  
Dismal Prognosis ◽  
Fatty Acid Beta Oxidation ◽  
Genome Scale

Pancreatic ductal adenocarcinoma (PDAC) is a major research focus due to its poor therapy response and dismal prognosis. PDAC cells adapt their metabolism efficiently to the environment to which they are exposed, often relying on diverse fuel sources depending on availability. Since traditional experimental techniques appear exhaustive in the search for a viable therapeutic strategy against PDAC, in this study, a highly curated and omics-informed genome-scale metabolic model of PDAC was reconstructed using patient-specific transcriptomic data. From the analysis of the model-predicted metabolic changes, several new metabolic functions were explored as potential therapeutic targets against PDAC in addition to the already known metabolic hallmarks of pancreatic cancer. Significant downregulation in the peroxisomal fatty acid beta oxidation pathway reactions, flux modulation in the carnitine shuttle system, and upregulation in the reactive oxygen species detoxification pathway reactions were observed. These unique metabolic traits of PDAC were then correlated with potential drug combinations that can be repurposed for targeting genes with poor prognosis in PDAC. Overall, these studies provide a better understanding of the metabolic vulnerabilities in PDAC and will lead to novel effective therapeutic strategies.

scholarly journals The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results

2010 ◽  
Vol 33 (5) ◽  
pp. 479-494 ◽  
Author(s):  
Ronald J. A. Wanders ◽  
Jos P. N. Ruiter ◽  
Lodewijk IJlst ◽  
Hans R. Waterham ◽  
Sander M. Houten
Keyword(s):  
Fatty Acid ◽  
Neonatal Screening ◽  
Beta Oxidation ◽  
Mitochondrial Fatty Acid ◽  
Fatty Acid Beta Oxidation

Effects of ATP precursors on ATP and free ADP content and functional recovery of postischemic hearts

1989 ◽  
Vol 256 (2) ◽  
pp. H560-H566 ◽  
Author(s):  
G. Ambrosio ◽  
W. E. Jacobus ◽  
M. C. Mitchell ◽  
M. R. Litt ◽  
L. C. Becker
Keyword(s):  
Functional Recovery ◽  
Adenine Nucleotide ◽  
Mean Value ◽  
Global Ischemia ◽  
Stunned Myocardium ◽  
Base Line ◽  
Atp Content ◽  
Atp Levels ◽  
Developed Pressure

It has been proposed that administration of adenine nucleotide precursors might accelerate replenishment of myocardial ATP and "free" ADP, thus improving recovery of depressed contractility of postischemic hearts. To test this hypothesis, Langendorff-perfused rabbit hearts were subjected to 20 min of global ischemia and reperfused for 2 h with normal perfusate (n = 8) or perfusate containing 100 mumol/l of the ATP precursors adenosine (n = 8) or 5-amino-4-imidazolecarboxamide riboside (AICAriboside; n = 8). After reperfusion, developed pressure in untreated hearts averaged 70-80% of base line, whereas ATP content was reduced to approximately 70% of preischemic values. AICAriboside administration did not increase tissue ATP levels or contractility. However, in every heart that received adenosine during reperfusion, ATP content increased from a mean value of 65 +/- 4% of base line to 84 +/- 5% at the end of reperfusion (P less than 0.001). Free ADP also increased in adenosine-treated hearts from 40 to 50% of base line at the beginning of reperfusion, to normal levels by 60 min. However, no improvement in contractility was observed in the hearts that received adenosine. These results support the hypothesis that decreased availability of nucleotide precursors is responsible for depressed ATP levels in postischemic hearts; however, reduced ATP and free ADP levels may not be directly responsible for the depressed function of stunned myocardium.

scholarly journals Oogenesis and lipid metabolism in the deep-sea sponge Phakellia ventilabrum: an histological, lipidomic and transcriptomic approach

2021 ◽  
Author(s):  
Vasiliki Koutsouveli ◽  
David Balgoma ◽  
Antonia Checa ◽  
Mikael Hedeland ◽  
Ana Riesgo ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Deep Sea ◽  
Expression Patterns ◽  
Rna Seq ◽  
Beta Oxidation ◽  
Animal Reproduction ◽  
Physiological Processes ◽  
Key Species ◽  
Fatty Acid Beta Oxidation

Abstract Background Sponges contain an astounding diversity of lipids which serve in several biological functions, including yolk formation in their oocytes and the embryos. On animal reproduction, lipids constitute one of the main energy storage forms for the adult and the offspring. The study of lipid metabolism during reproduction can provide information on food-web dynamics and energetic needs of the populations in their habitats, however, there are no studies focusing on the lipid metabolism of sponges during seasonal reproduction. The deep-sea sponge Phakellia ventilabrum (Demospongiae, Bubarida) is a key species of North-Atlantic sponge grounds, but its reproductive biology is not known. In this study, we used histological sections, lipidome profiling (UHPLC-MS), and transcriptomic analysis (RNA-seq) with goal to i. assess the reproductive strategy and seasonality of this species, ii. examine the relative changes in the lipidome signal, and the gene expression patterns (RNA-seq) of enzymes participating in lipid metabolism in female specimens during gametogenesis.Results P. ventilabrum is an oviparous and most certainly gonochoristic species, reproducing in May and September in the different studied areas. Half of specimens were reproducing, generating two to five oocytes per mm2. Oocytes accumulated both protein and lipid droplets. As oogenesis progressed, the signal of most of the unsaturated and monounsaturated triacylglycerides increased, as well as of few other phospholipids. Most of the other lipids and especially those with > 3 unsaturations showed a decrease in signal during the oocyte maturation. In parallel, we detected upregulated genes in female tissues related to triacylglyceride biosynthesis and others related to fatty acid beta-oxidation.Conclusions Triacylglycerides are probably the main type of lipid forming the yolk since this lipid category has the most marked changes, while some other phospholipids may also have a role in oogenesis. In parallel, other lipid categories were oxidized, leading to fatty acid beta-oxidation to cover the energy requirements of female individuals during oogenesis. Variations in the signal of most lipids between the different locations and months suggest that sponges, apart from their own mechanisms of lipid biosynthesis, exploit the food availability in their surroundings to cover the energetic demands in their physiological processes.

scholarly journals Succession of physiological stages hallmarks the transcriptomic response of fungus Aspergillus niger to lignocellulose

2019 ◽  
Author(s):  
Jolanda M. van Munster ◽  
Paul Daly ◽  
Martin J. Blythe ◽  
Roger Ibbett ◽  
Matt Kokolski ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Wheat Straw ◽  
Hydrolytic Enzymes ◽  
Life Time ◽  
Gene Clusters ◽  
Biofuel Production ◽  
Beta Oxidation ◽  
Transcriptomic Response ◽  
Initial Exposure ◽  
Fatty Acid Beta Oxidation

AbstractBackgroundUnderstanding how fungi degrade lignocellulose is a cornerstone of improving renewables-based biotechnology, in particular for the production of hydrolytic enzymes. Considerable progress has been made in investigating fungal degradation during time-points where CAZyme expression peaks. However, a robust understanding of the fungal survival strategies over its life time on lignocellulose is thereby missed. Here we aimed to uncover the physiological responses of the biotechnological workhorse and enzyme producer Aspergilllus niger over its life time to six substrates important for biofuel production.ResultsWe analysed the response of A. niger to the feedstock Miscanthus and compared it with our previous study on wheat straw, alone or in combination with hydrothermal or ionic liquid feedstock pretreatments. Conserved (substrate-independent) metabolic responses as well as those affected by pretreatment and feedstock were identified via multivariate analysis of genome-wide transcriptomics combined with targeted transcript and protein analyses and mapping to a metabolic model. Initial exposure to all substrates increased fatty acid beta-oxidation and lipid metabolism transcripts. In a strain carrying a deletion of the ortholog of the Aspergillus nidulans fatty acid beta-oxidation transcriptional regulator farA, there was a reduction in expression of selected lignocellulose degradative CAZyme-encoding genes suggesting that beta-oxidation contributes to adaptation to lignocellulose. Mannan degradation expression was wheat straw feedstock-dependent and pectin degradation was higher on the untreated substrates. In the later life stages, known and novel secondary metabolite gene clusters were activated, which are of high interest due to their potential to synthesize bioactive compounds.ConclusionIn this study, which includes the first transcriptional response of Aspergilli to Miscanthus, we highlighted that life time as well as substrate composition and structure (via variations in pretreatment and feedstock) influence the fungal responses to lignocellulose. We also demonstrated that the fungal response contains physiological stages that are conserved across substrates and are typically found outside of the conditions with high CAZyme expression, as exemplified by the stages that are dominated by lipid and secondary metabolism.

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