Category: 97-67-6

Lee, Richard G. published the artcileCardiolipin is required for membrane docking of mitochondrial ribosomes and protein synthesis, Application of (S)-2-hydroxysuccinic acid, the main research area is cardiolipin mitochondrial ribosome protein synthesis membrane docking; Cardiolipin; Mitochondrial membrane; Mitochondrial ribosomes; Protein synthesis.

The mitochondrial inner membrane contains a unique phospholipid known as cardiolipin (CL), which stabilizes the protein complexes embedded in the membrane and supports its overall structure. Recent evidence indicates that the mitochondrial ribosome may associate with the inner membrane to facilitate co-translational insertion of the hydrophobic oxidative phosphorylation (OXPHOS) proteins into the inner membrane. We generated three mutant knockout cell lines for the CL biosynthesis gene Crls1 to investigate the effects of CL loss on mitochondrial protein synthesis. Reduced CL levels caused altered mitochondrial morphol. and transcriptome-wide changes that were accompanied by uncoordinated mitochondrial translation rates and impaired respiratory chain supercomplex formation. Aberrant protein synthesis was caused by impaired formation and distribution of mitochondrial ribosomes. Reduction or loss of CL resulted in divergent mitochondrial and endoplasmic reticulum stress responses. We show that CL is required to stabilize the interaction of the mitochondrial ribosome with the membrane via its association with OXA1 (also known as OXA1L) during active translation. This interaction facilitates insertion of newly synthesized mitochondrial proteins into the inner membrane and stabilizes the respiratory supercomplexes.

Journal of Cell Science published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (Agpat5). 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Application of (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Ravi, Archna published the artcilePI5P4Ks drive metabolic homeostasis through peroxisome-mitochondria interplay, Recommanded Product: (S)-2-hydroxysuccinic acid, the main research area is PIPK metabolic homeostasis peroxisome mitochondria interplay; PI-4,5-P(2); PI-5-P; PI5P4Ks; cancer; fatty acid; lipid; lipid droplet; metabolism; mitochondria; peroxisome; phosphoinositide; phosphoinositide kinase; sarcoma; β-oxidation.

PI5P4Ks are a class of phosphoinositide kinases that phosphorylate PI-5-P to PI-4,5-P2. Distinct localization of phosphoinositides is fundamental for a multitude of cellular functions. Here, we identify a role for peroxisomal PI-4,5-P2 generated by the PI5P4Ks in maintaining energy balance. We demonstrate that PI-4,5-P2 regulates peroxisomal fatty acid oxidation by mediating trafficking of lipid droplets to peroxisomes, which is essential for sustaining mitochondrial metabolism Using fluorescent-tagged lipids and metabolite tracing, we show that loss of the PI5P4Ks significantly impairs lipid uptake and b-oxidation in the mitochondria. Further, loss of PI5P4Ks results in dramatic alterations in mitochondrial structural and functional integrity, which under nutrient deprivation is further exacerbated, causing cell death. Notably, inhibition of the PI5P4Ks in cancer cells and mouse tumor models leads to decreased cell viability and tumor growth, resp. Together, these studies reveal an unexplored role for PI5P4Ks in preserving metabolic homeostasis, which is necessary for tumorigenesis.

Developmental Cell published new progress about Cell death. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Recommanded Product: (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Molteni, Raffaella published the artcileOncogene-induced maladaptive activation of trained immunity in the pathogenesis and treatment of Erdheim-Chester disease, Recommanded Product: (S)-2-hydroxysuccinic acid, the main research area is oncogene trained immunity erdheim chester disease.

Trained immunity (TI) is a proinflammatory program induced in monocyte/macrophages upon sensing of specific pathogens and is characterized by immunometabolic and epigenetic changes that enhance cytokine production Maladaptive activation of TI (ie, in the absence of infection) may result in detrimental inflammation and development of disease; however, the exact role and extent of inappropriate activation of TI in the pathogenesis of human diseases is undetermined In this study, we uncovered the oncogene-induced, maladaptive induction of TI in the pathogenesis of a human inflammatory myeloid neoplasm (Erdheim-Chester disease, [ECD]), characterized by the BRAFV600E oncogenic mutation in monocyte/macrophages and excess cytokine production Mechanistically, myeloid cells expressing BRAFV600E exhibit all mol. features of TI: activation of the AKT/mammalian target of rapamycin signaling axis; increased glycolysis, glutaminolysis, and cholesterol synthesis; epigenetic changes on promoters of genes encoding cytokines; and enhanced cytokine production leading to hyperinflammatory responses. In patients with ECD, effective therapeutic strategies combat this maladaptive TI phenotype; in addition, pharmacol. inhibition of immunometabolic changes underlying TI (ie, glycolysis) effectively dampens cytokine production by myeloid cells. This study revealed the deleterious potential of inappropriate activation of TI in the pathogenesis of human inflammatory myeloid neoplasms and the opportunity for inhibition of TI in conditions characterized by maladaptive myeloid-driven inflammation.

Blood published new progress about Cell differentiation. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Recommanded Product: (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Feliciano, Patricia R. published the artcileStructural and Biochemical Investigations of the [4Fe-4S] Cluster-Containing Fumarate Hydratase from Leishmania major, Recommanded Product: (S)-2-hydroxysuccinic acid, the main research area is cluster 4Fe4S containing fumarate hydratase Leishmania crystal structure.

Class I fumarate hydratases (FHs) are central metabolic enzymes that use a [4Fe-4S] cluster to catalyze the reversible conversion of fumarate to S-malate. The parasite Leishmania major, which is responsible for leishmaniasis, expresses two class I FH isoforms: mitochondrial LmFH-1 and cytosolic LmFH-2. In this study, we present kinetic characterizations of both LmFH isoforms, present thirteen crystal structures of LmFH-2 variants, and employ site-directed mutagenesis to investigate the enzyme’s mechanism. Our kinetic data confirm that both LmFH-1 and LmFH-2 are susceptible to oxygen-dependent inhibition, with data from crystallog. and ESR spectroscopy showing that oxygen exposure converts an active [4Fe-4S] cluster to an inactive [3Fe-4S] cluster. Our anaerobically-conducted kinetic studies reveal a preference for fumarate over S-malate. Our data further reveal that single alanine substitutions of T467, R421, R471, D135, and H334 decrease kcat 9-fold to 16,000-fold without substantially affecting Km, suggesting that these residues function in catalytic roles. Crystal structures of LmFH-2 variants are consistent with this idea, showing similar bidentate binding to the unique iron of the [4Fe-4S] cluster for substrate S-malate as observed in wild type FH. We further present LmFH-2 structures with substrate fumarate and weak inhibitors succinate and malonate bound in the active site, and the first structure of an LmFH that is substrate-free and inhibitor-free, the latter showing increased mobility of the C-terminal domain. Collectively, these data provide insight into the mol. basis for the reaction catalyzed by LmFHs, enzymes that are potential drug targets against leishmaniasis.

Biochemistry published new progress about Crystal structure. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Recommanded Product: (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Isaacs-Ten, Anna published the artcileMetabolic Regulation of Macrophages by SIRT1 Determines Activation During Cholestatic Liver Disease in Mice, Synthetic Route of 97-67-6, the main research area is cholestatic liver disease autophagy SIRT1 macrophage metabolic regulation; Cholestasis; Inflammasome; Macrophages; Metabolism; SIRT1.

Inflammation is the hallmark of chronic liver disease. Metabolism is a key determinant to regulate the activation of immune cells. Here, we define the role of sirtuin 1 (SIRT1), a main metabolic regulator, in controlling the activation of macrophages during cholestatic liver disease and in response to endotoxin. We have used mice overexpressing SIRT1, which we treated with i.p. lipopolysaccharides or induced cholestasis by bile duct ligation. Bone marrow-derived macrophages were used for mechanistic in vitro studies. Finally, PEPC-Boy mice were used for adoptive transfer experiments to elucidate the impact of SIRT1-overexpressing macrophages in contributing to cholestatic liver disease. We found that SIRT1 overexpression promotes increased liver inflammation and liver injury after lipopolysaccharide/GalN and bile duct ligation; this was associated with an increased activation of the inflammasome in macrophages. Mechanistically, SIRT1 overexpression associated with the activation of the mammalian target of rapamycin (mTOR) pathway that led to increased activation of macrophages, which showed metabolic rewiring with increased glycolysis and broken tricarboxylic acid cycle in response to endotoxin in vitro. Activation of the SIRT1/mTOR axis in macrophages associated with the activation of the inflammasome and the attenuation of autophagy. Ultimately, in an in vivo model of cholestatic disease, the transplantation of SIRT1-overexpressing myeloid cells contributed to liver injury and fibrosis. Our study provides novel mechanistic insights into the regulation of macrophages during cholestatic disease and the response to endotoxin, in which the SIRT1/mTOR crosstalk regulates macrophage activation controlling the inflammasome, autophagy and metabolic rewiring.

Cellular and Molecular Gastroenterology and Hepatology published new progress about Apoptosis. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Synthetic Route of 97-67-6.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Hayasaka, Kiyoshi published the artcileMetabolic basis and treatment of citrin deficiency, Name: (S)-2-hydroxysuccinic acid, the main research area is review citrin deficiency medium chain triglyceride supplement; adult-onset type II citrullinemia (CTLN2); citrin deficiency; failure to thrive and dyslipidemia by citrin deficiency (FTTDCD); medium-chain triglyceride (MCT); neonatal intrahepatic cholestasis by citrin deficiency (NICCD).

Citrin deficiency is a hereditary disorder caused by SLC25A13 mutations and manifests as neonatal intrahepatic cholestasis (NICCD), failure to thrive and dyslipidemia (FTTDCD), and adult-onset type II citrullinemia (CTLN2). Citrin is a component of the malate-aspartate NAD hydrogen (NADH) shuttle, an essential shuttle for hepatic glycolysis. Hepatic glycolysis and the coupled lipogenesis are impaired in citrin deficiency. Hepatic lipogenesis plays a significant role in fat supply during growth spurt periods: the fetal period, infancy, and puberty. Growth impairment in these periods is characteristic of citrin deficiency. Hepatocytes with citrin deficiency cannot use glucose and fatty acids as energy sources due to defects in the NADH shuttle and downregulation of peroxisome proliferator-activated receptor α (PPARα), resp. An energy deficit in hepatocytes is considered a fundamental pathogenesis of citrin deficiency. Medium-chain triglyceride (MCT) supplementation with a lactose-restricted formula and MCT supplementation under a low-carbohydrate diet are recommended for NICCD and CTLN2, resp. MCT supplementation therapy can provide energy to hepatocytes, promote lipogenesis, correct the cytosolic NAD+/NADH ratio via the malate-citrate shuttle and improve ammonia detoxification, and it is a reasonable therapy for citrin deficiency. It is very important to administer MCT at a dose equivalent to the liver’s energy requirements in divided doses with meals. MCT supplementation therapy is certainly promising for promoting growth spurts during infancy and adolescence and for preventing CTLN2 onset. I.v. administration of solutions containing fructose is contraindicated, and persistent hyperglycemia should be avoided due to glucose intoxication for patients receiving hyperalimentation or with complicating diabetes.

Journal of Inherited Metabolic Disease published new progress about Diabetes mellitus. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Name: (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Lee, Wen-Chih published the artcileMalic Enzyme Couples Mitochondria with Aerobic Glycolysis in Osteoblasts, Name: (S)-2-hydroxysuccinic acid, the main research area is malic enzyme couple mitochondria aerobic glycolysis osteoblast; TCA cycle; aerobic glycolysis; bone; differentiation; malate-aspartate shuttle; malic enzyme; metabolic tracing; metabolism; mitochondria; osteoblast.

The metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen consumption. As a result, aerobic glycolysis accounts for approx. 80% of the ATP production in mature osteoblasts. In vivo tracing with 13C-labeled glucose in the mouse shows that glucose in bone is readily metabolized to lactate but not organic acids in the TCA cycle. Glucose tracing in osteoblast cultures reveals that pyruvate is carboxylated to form malate integral to the malate-aspartate shuttle. RNA sequencing (RNA-seq) identifies Me2, encoding the mitochondrial NAD-dependent isoform of malic enzyme, as being specifically upregulated during osteoblast differentiation. Knockdown of Me2 markedly reduces the glycolytic flux and impairs osteoblast proliferation and differentiation. Thus, the mitochondrial malic enzyme functionally couples the mitochondria with aerobic glycolysis in osteoblasts.

Cell Reports published new progress about Cell differentiation. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Name: (S)-2-hydroxysuccinic acid.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Mendonca, Caroll M. published the artcileHierarchical routing in carbon metabolism favors iron-scavenging strategy in iron-deficient soil Pseudomonas species, Synthetic Route of 97-67-6, the main research area is iron carbon metabolome Pseudomonas; Pseudomonas putida; bacteria; iron limitation; metabolomics; siderophore.

High-affinity iron (Fe) scavenging compounds, or siderophores, are widely employed by soil bacteria to survive scarcity in bioavailable Fe. Siderophore biosynthesis relies on cellular carbon metabolism, despite reported decrease in both carbon uptake and Fe-containing metabolic proteins in Fe-deficient cells. Given this paradox, the metabolic network required to sustain the Fe-scavenging strategy is poorly understood. Here, through multiple 13C-metabolomics experiments with Fe-replete and Fe-limited cells, we uncover how soil Pseudomonas species reprogram their metabolic pathways to prioritize siderophore biosynthesis. Across the three species investigated (Pseudomonas putida KT2440, Pseudomonas protegens Pf-5, and Pseudomonas putida S12), siderophore secretion is higher during growth on gluconeogenic substrates than during growth on glycolytic substrates. In response to Fe limitation, we capture decreased flux toward the tricarboxylic acid (TCA) cycle during the metabolism of glycolytic substrates but, due to carbon recycling to the TCA cycle via enhanced anaplerosis, the metabolism of gluconeogenic substrates results in an increase in both siderophore secretion (up to threefold) and Fe extraction (up to sixfold) from soil minerals. During simultaneous feeding on the different substrate types, Fe deficiency triggers a hierarchy in substrate utilization, which is facilitated by changes in protein abundances for substrate uptake and initial catabolism. Rerouted metabolism further promotes favorable fluxes in the TCA cycle and the gluconeogenesis-anaplerosis nodes, despite decrease in several proteins in these pathways, to meet carbon and energy demands for siderophore precursors in accordance with increased proteins for siderophore biosynthesis. Hierarchical carbon metabolism thus serves as a critical survival strategy during the metal nutrient deficiency.

Proceedings of the National Academy of Sciences of the United States of America published new progress about Carbon metabolic pathway. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Synthetic Route of 97-67-6.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Garcia, Amanda Carvalho published the artcileBacterial small RNAs in the genus Herbaspirillum spp, Related Products of alcohols-buliding-blocks, the main research area is Herbaspirillum small non coding RNA rimP gene CRISPR; CRISPR; RNA non-coding (ncRNA); mRNA; ncRNA cis-encoded; riboswitches; trans-encoded.

The genus Herbaspirillum includes several strains isolated from different grasses. The identification of non-coding RNAs (ncRNAs) in the genus Herbaspirillum is an important stage studying the interaction of these mols. and the way they modulate physiol. responses of different mechanisms, through RNA-RNA interaction or RNA-protein interaction. This interaction with their target occurs through the perfect pairing of short sequences (cis-encoded ncRNAs) or by the partial pairing of short sequences (trans-encoded ncRNAs). However, the companion Hfq can stabilize interactions in the trans-acting class. In addition, there are Riboswitches, located at the 5′ end of mRNA and less often at the 3′ end, which respond to environmental signals, high temperatures, or small binder mols. Recently, CRISPR (clustered regularly interspaced palindromic repeats), in prokaryotes, have been described that consist of serial repeats of base sequences (spacer DNA) resulting from a previous exposure to exogenous plasmids or bacteriophages. We identified 285 ncRNAs in Herbaspirillum seropedicae (H. seropedicae) SmR1, expressed in different exptl. conditions of RNA-seq material, classified as cis-encoded ncRNAs or trans-encoded ncRNAs and detected RNA riboswitch domains and CRISPR sequences. The results provide a better understanding of the participation of this type of RNA in the regulation of the metabolism of bacteria of the genus Herbaspirillum spp.

International Journal of Molecular Sciences published new progress about Flavonoids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Related Products of alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts

Long, Nguyen Phuoc published the artcileIsolation and Metabolic Assessment of Cancer Cell Mitochondria, Category: alcohols-buliding-blocks, the main research area is metabolism cancer cell mitochondria.

Mitochondrial metabolism plays an essential role in various biol. processes of cancer cells. Herein, the authors established an exptl. procedure for the metabolic assessment of mitochondria in cancer cells. The authors examined procedures for mitochondrial isolation coupled with various mitochondrial extraction buffers in three major cancer cell lines (PANC1, A549, and MDA-MB-231) and identified a potentially optimal and generalized approach. The purity of the mitochondrial fraction isolated by the selected protocol was verified using specific protein markers of cellular components, and the ultrastructure of the isolated mitochondria was also analyzed by TEM. The isolation procedure, involving a bead beater for cell lysis, a modified sucrose buffer, and differential centrifugation, appeared to be a suitable method for the extraction of mitochondria from cancer cells. Electron micrographs indicated an intact two-layer membrane and inner structures of mitochondria isolated by this procedure. Metabolomic and lipidomic analyses were conducted to examine the metabolic phenotypes of the mitochondria-enriched fractions and associated bulk cancer cells. A total of 44 metabolites, including malate and succinate, occurred at significantly higher levels in the mitochondrial fractions, whereas 51 metabolites, including citrate, oxaloacetate, and fumarate of the Krebs cycle and the oncometabolites glutamine and glutamate, were reduced in mitochondria compared to that in the corresponding bulk cells of PANC1. Similar patterns were observed in mitochondria and bulk cells of MDA-MB-231 and A549 cell lines. A clear difference between the lipid profiles of bulk PANC1, MDA-MB-231, and A549 and corresponding mitochondrial fractions of these cell lines was detected by principal component anal. In conclusion, the authors developed an exptl. procedure for a large-scale metabolic assessment for suborganelle metabolic profiling and multiple omics data integration in cancer cells with broad applications.

ACS Omega published new progress about Biomarkers. 97-67-6 belongs to class alcohols-buliding-blocks, name is (S)-2-hydroxysuccinic acid, and the molecular formula is C4H6O5, Category: alcohols-buliding-blocks.

Referemce:
Alcohol – Wikipedia,
Alcohols – Chemistry LibreTexts