Structure of a NADH-Insensitive Hexameric Citrate Synthase that Resists Acid Inactivation†

Biochemistry ◽  
2006 ◽  
Vol 45 (45) ◽  
pp. 13487-13499 ◽  
Author(s):  
Julie A. Francois ◽  
Courtney M. Starks ◽  
Sasitorn Sivanuntakorn ◽  
Hong Jiang ◽  
Aaron E. Ransome ◽  
...  
Keyword(s):  
Citrate Synthase ◽  
Acid Inactivation

Identification of binding partners of CsaA - an archaeal chaperonic pro-tein of Picrophilus torridus

2020 ◽  
Vol 27 ◽  
Author(s):  
Neelja Singhal ◽  
Archana Sharma ◽  
Manisha Aswal ◽  
Nirpendra Singh ◽  
Manish Kumar ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Citrate Synthase ◽  
Elongation Factor ◽  
Trna Synthetase ◽  
Strong Interactions ◽  
Beta Chain ◽  
Protein Protein Interactions ◽  
Uncharacterized Protein ◽  
Binding Partners ◽  
Picrophilus Torridus

Background:: CsaA is among the few chaperones which are present in both bacteria and archaea, but absent in eukaryotes. There are no reports on interactome analysis of CsaA from archaea, till date. Identification of binding partners of CsaA might be helpful in understanding CsaA-associated processes in Picrophilus torridus– an extreme thermoaci-dophilic euryarchaeon. Objectives:: The present study was conducted to identify the binding partners of CsaA of P. torridus (PtCsaA). Methods:: The binding partners of PtCsaA were isolated and identified using a pull down assay and liquid chromatography-mass spectrometry (LC-MS). Results:: The results revealed twelve potential binding partners of CsaA. These were thermosome subunits (Q6KZS2 and Q6L132), nascent polypeptide-associated complex protein (Q6L1N3), elongation factor 1-alpha (Q6L202), uncharacterized protein (Q6L0Y6), citrate synthase (Q6L0M8), asparaginyl-tRNA synthetase (Q6L0M5), succinyl-CoA synthetase beta chain (Q6L0B4), pyruvate ferredoxin oxidoreductase alpha and beta chain proteins (Q6KZA7 and Q6KZA6, respectively), malate dehydrogenase (Q6L0C3) and reversed fumarylacetoacetase (Q6KZ97). Functional categorization revealed that of these, six proteins were involved in energy metabolic pathways, three were archaeal chaperones, two were involved in trans-lation and one might be a transcription regulator. STRING-based analysis of the protein-protein interactions of the experi-mental interactome revealed strong interactions among them. Conclusion:: PtCsaA might be a multifaceted protein which besides translation might also play important role in metabolic processes of P. torridus. However, further experiments investigating the binding partners of CsaA in other archaea are re-quired for a better understanding of CsaA-associated processes in archaea.

Role of Quercetin in Mitigation of Lindane Induced Toxicity in Terms of Oxidative Responses and Metabolic Status in Mice Brain

2020 ◽  
Vol 16 ◽  
Author(s):  
Anupama Sharma ◽  
Renu Bist ◽  
Hemant Pareek
Keyword(s):  
Citrate Synthase ◽  
Thiobarbituric Acid ◽  
Tca Cycle ◽  
Treated Group ◽  
Protein Carbonyl ◽  
Protein Carbonyl Content ◽  
Mice Brain ◽  
The Brain ◽  
Oxidative Responses

Background:: Current study evaluated the protective potential of quercetin against lindane induced toxicity in mice brain. For investigation, mice were allocated into four groups; First group was control. Second group was administered with oral dose of lindane (25 mg/kg bw) for 4 consecutive days. Third group was exposed to quercetin (40 mg/kg bw) and in fourth group, quercetin was administered 1 hour prior to the exposure of lindane. Objective:: Two major objectives were decided for study. First was to create lesions in the brain by lindane and; second was to evaluate the neuroprotective potential of quercetin. Methods:: To study oxidative responses, level of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), reduced glutathione (GSH), superoxide dismutase (SOD), Catalase (CAT), and glutathione peroxidase (GPx) were measured in brain homogenates. Three key step regulating enzymes of tricarboxylic acid (TCA) cycle viz citrate synthase (CS), pyruvate dehydrogenase (PDH) and fumarase were also assayed. Results:: Lindane treatment significantly enhanced the levels of TBARS (P<0.001),PCC (P<0.001), GPx (P<0.001), SOD (P<0.05), PDH (P<0.05) and fumarase (P<0.001) in brains of mice compared to control. Meanwhile, it alleviated GSH, CAT and CS (P<0.05) activity. Conclusion:: Pretreatment with quercetin in lindane treated group not only restored, previously altered biochemical parameters after lindane treatment and also significantly improved them too which suggests that quercetin is not only invulnerable rather neuroprotective against lindane intoxication.

Schisandrin Restores the Amyloid β-Induced Impairments on Mitochondrial Function, Energy Metabolism, Biogenesis, and Dynamics in Rat Primary Hippocampal Neurons

Pharmacology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Zhongyuan Piao ◽  
Lin Song ◽  
Lifen Yao ◽  
Limei Zhang ◽  
Yichan Lu
Keyword(s):  
Energy Metabolism ◽  
Cytochrome C ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Function ◽  
Hippocampal Neurons ◽  
Citrate Synthase ◽  
Mitochondrial Permeability Transition ◽  
Amyloid Β ◽  
Mitochondrial Functions ◽  
Primary Hippocampal Neurons

Introduction: Schisandrin which is derived from Schisandra chinensis has shown multiple pharmacological effects on various diseases including Alzheimer’s disease (AD). It is demonstrated that mitochondrial dysfunction plays an essential role in the pathogenesis of neurodegenerative disorders. Objective: Our study aims to investigate the effects of schisandrin on mitochondrial functions and metabolisms in primary hippocampal neurons. Methods: In our study, rat primary hippocampal neurons were isolated and treated with indicated dose of amyloid β1–42 (Aβ1–42) oligomer to establish a cell model of AD in vitro. Schisandrin (2 μg/mL) was further subjected to test its effects on mitochondrial function, energy metabolism, mitochondrial biogenesis, and dynamics in the Aβ1–42 oligomer-treated neurons. Results and Conclusions: Our findings indicated that schisandrin significantly alleviated the Aβ1–42 oligomer-induced loss of mitochondrial membrane potential and impaired cytochrome c oxidase activity. Additionally, the opening of mitochondrial permeability transition pore and release of cytochrome c were highly restricted with schisandrin treatment. Alterations in cell viability, ATP production, citrate synthase activity, and the expressions of glycolysis-related enzymes demonstrated the relief of defective energy metabolism in Aβ-treated neurons after the treatment of schisandrin. For mitochondrial biogenesis, elevated expression of peroxisome proliferator-activated receptor γ coactivator along with promoted mitochondrial mass was found in schisandrin-treated cells. The imbalance in the cycle of fusion and fission was also remarkably restored by schisandrin. In summary, this study provides novel mechanisms for the protective effect of schisandrin on mitochondria-related functions.

scholarly journals The Hsp60 Protein of Helicobacter Pylori Exhibits Chaperone and ATPase Activities at Elevated Temperatures

BioChem ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 19-25
Author(s):  
Jose A. Mendoza ◽  
Julian L. Ignacio ◽  
Christopher M. Buckley
Keyword(s):  
Helicobacter Pylori ◽  
Heat Stress ◽  
Molecular Chaperone ◽  
Elevated Temperatures ◽  
Citrate Synthase ◽  
Gastric Epithelium ◽  
Acidic Conditions ◽  
H Pylori ◽  
Induced Aggregation ◽  
Hydrolysis Of

The heat-shock protein, Hsp60, is one of the most abundant proteins in Helicobacter pylori. Given its sequence homology to the Escherichia coli Hsp60 or GroEL, Hsp60 from H. pylori would be expected to function as a molecular chaperone in this organism. H. pylori is a type of bacteria that grows on the gastric epithelium, where the pH can fluctuate between neutral and 4.5, and the intracellular pH can be as low as 5.0. We previously showed that Hsp60 functions as a chaperone under acidic conditions. However, no reports have been made on the ability of Hsp60 to function as a molecular chaperone under other stressful conditions, such as heat stress or elevated temperatures. We report here that Hsp60 could suppress the heat-induced aggregation of the enzymes rhodanese, malate dehydrogenase, citrate synthase, and lactate dehydrogenase. Moreover, Hsp60 was found to have a potassium and magnesium-dependent ATPase activity that was stimulated at elevated temperatures. Although, Hsp60 was found to bind GTP, the hydrolysis of this nucleotide could not be observed. Our results show that Hsp60 from H. pylori can function as a molecular chaperone under conditions of heat stress.

scholarly journals The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

2021 ◽  
Vol 22 (4) ◽  
pp. 1665
Author(s):  
Guglielmina Chimienti ◽  
Anna Picca ◽  
Flavio Fracasso ◽  
Francesco Russo ◽  
Antonella Orlando ◽  
...  
Keyword(s):  
Calorie Restriction ◽  
Citrate Synthase ◽  
Aging Effect ◽  
Mtdna Damage ◽  
Mitochondrial Markers ◽  
Age Related ◽  
Efficacious Treatment ◽  
Mtdna Deletion ◽  
Cyt C ◽  
Ad Libitum

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.

scholarly journals 145 President Oral Presentation Pick: Prenatal stress increases skeletal muscle mitochondrial volume density and function in yearling Brahman calves

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 120-121
Author(s):  
Chloey P Guy ◽  
Catherine L Wellman ◽  
David G Riley ◽  
Charles R Long ◽  
Ron D Randel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Creatine Kinase ◽  
Muscle Damage ◽  
Prenatal Stress ◽  
Citrate Synthase ◽  
Volume Density ◽  
Assembly Factor ◽  
Mitochondrial Volume ◽  
Mitochondrial Volume Density ◽  
And Function

Abstract We previously determined that prenatal stress (PNS) differentially affected methylation of DNA from leukocytes of 28-d-old calves. Specifically, COX14 (cytochrome c oxidase (COX) assembly factor) and CKMT1B (mitochondrial creatine kinase U-type) were hypomethylated and COA5 (COX assembly factor 5), COX5A (COX subunit 5A), NRF1 (nuclear respiratory factor 1), and GSST1 (glutathione S-transferase theta-1) were hypermethylated in PNS compared to non-PNS calves (P ≤ 0.05). Our current objective was to test the hypothesis that PNS exhibit impaired mitochondrial function and greater oxidative stress than non-PNS calves. Blood and longissimus dorsi muscle samples were collected from yearling Brahman calves whose mothers were stressed by 2 h transportation at 60, 80, 100, 120, and 140 days of gestation (PNS; 8 bulls, 6 heifers) and non-PNS calves (4 bulls, 6 heifers). Serum was evaluated for the stress hormone, cortisol, and muscle damage marker, creatine kinase; muscle was analyzed for mitochondrial volume density and function by citrate synthase (CS) and COX activities, respectively, concentration of malondialdehyde, a lipid peroxidation marker, and activity of the antioxidant, superoxide dismutase (SOD). Data were analyzed using mixed linear models with treatment and sex as fixed effects. Serum cortisol was numerically higher in PNS than non-PNS calves but was not statistically different. Muscle CS and COX activities relative to protein were greater in PNS than non-PNS calves (P ≤ 0.03), but COX relative to CS activity was similar between groups. Activity of COX was greater in bulls than heifers (P = 0.03), but no other measure was affected by sex. All other measures were unaffected by PNS. Prenatal stress did not affect markers of muscle damage and oxidative stress in yearling Brahman calves at rest but mitochondrial volume density and function were greater in PNS calves. Acute stressors induce oxidative stress, so implications of differences in mitochondria in PNS calves following a stressor should be investigated.

Acetyl-CoA is produced by the citrate synthase homology module of ATP-citrate lyase

2021 ◽  
Author(s):  
Kenneth Verstraete ◽  
Koen H. G. Verschueren ◽  
Ann Dansercoer ◽  
Savvas N. Savvides
Keyword(s):  
Citrate Synthase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Homology Module
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