• AGK also has an implicated role in the assembly of the adenine nucleotide translocator in the inner mitochondrial membrane. (wikipedia.org)
  • As phosphatidic acid is also involved in the synthesis of phospholipids, its loss will result in changes to the lipid composition of the inner mitochondrial membrane. (wikipedia.org)
  • Mitochondrial fusion is regulated by the large GTPases mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2), which fuse the OMM, and optic atrophy 1 (OPA-1), which fuses the inner mitochondrial membrane. (bvsalud.org)
  • Reducing equivalents produced in the Krebs cycle and in the beta-oxidation spirals are passed along a series of protein complexes embedded in the inner mitochondrial membrane (the electron transport chain). (medlink.com)
  • In healthy cells, the inner mitochondrial membrane where the electron transport system is located is mostly impermeable, and this is important in establishing trans-membrane chemical/electrical potential essential for energy production. (lifestylematrix.com)
  • Damage to mitochondrial components, especially the delicate inner mitochondrial membrane, leads to the release of toxic proteins that go through several steps to trigger the formation of the inflammatory molecular complex called an inflammasome. (lifestylematrix.com)
  • Phospholipase D in the signaling networks of plant response to abscisic acid and reactive oxygen species[J]. Biochimica et Biophysica Acta(BBA)-Molecular and Cell Biology of Lipids,2005,1736(1):1-9. (nefu.edu.cn)
  • Further biochemical analysis revealed that PPARγ-mediated lipid synthesis depletes nicotinamide adenine dinucleotide phosphate (NADPH), consequently resulting in increased mitochondrial reactive oxygen species (ROS) level that subsequently disrupted REDOX balance in lung cancer. (oncotarget.com)
  • Here, we show that formation of mitochondrial diacylglycerol (DAG) and its binding to PKD1 is the means by which PKD1 is localized to the mitochondria in response to ROS. (biologists.com)
  • For example, mice that are defective in mitochondrial fusion die during early development while yeast fusion mutants rapidly lose their mitochondria genome and become incapable of oxidative phosphorylation. (jhmi.edu)
  • The goals of our research are to understand the molecular basis of mitochondria fusion using biochemical approaches and to determine the physiological roles of mitochondrial fusion using cell culture and animal models. (jhmi.edu)
  • The mitochondrial membrane contains the major classes of phospholipids found in all cell membranes, including phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), and phosphatidic acid (PA), as well as phosphatidylglycerol (PG), the precursor for cardiolipin (CL), which is predominantly located in the mitochondria. (lifestylematrix.com)
  • Age-related gene expression profiles of the short-lived model animals Caenorhabditis elegans and Drosophila melanogaster share a common adult-onset expression program of genes involved in mitochondrial metabolism, DNA repair, catabolism, peptidolysis and cellular transport 3 . (nature.com)
  • The reduced expression of genes involved in mitochondrial oxidative respiration occurs in early adulthood, before the onset of functional decline, and more abruptly than a damage-response model would predict, which supports the possibility of programmed age-related transcriptional regulation 3 . (nature.com)
  • PGC-1α and PPARα are both master regulators of genes involved in mitochondrial biogenesis and fatty acid oxidation, respectively [reviewed in 6]. (aocs.org)
  • Oral MLR prevents oxidative damage, replaces damaged membrane phospholipids and maintains mitochondrial membrane permeability in the optimal range. (lifestylematrix.com)
  • Hence, the activity of mammalian glucose transporter depends upon anionic (phosphatidic acid, phosphatidylserine, phosphatidylglycerol, and phosphatidylinositol) and conical phospholipids (phosphatidylethanolamine and diacylglycerol) [265]. (nicotinic-receptor.com)
  • Furthermore, two intermediates in this pathway, phosphatidic acid and diacylglycerol, serve as essential precursors for the synthesis of phospholipids. (aocs.org)
  • Phospholipids are derivatives of glycerol-3-phosphate in which the glycerol backbone is attached to two fatty acids on one end and esterified phosphoric acid and an organic alcoholic group on the other. (microbenotes.com)
  • Phosphatidic acid is considered to be the precursor to many phospholipids. (microbenotes.com)
  • The protein encoded by this gene is a mitochondrial membrane protein involved in lipid and glycerolipid metabolism. (wikipedia.org)
  • This study aimed to explore the link between progesterone, a key steroid hormone produced by placenta, and mitochondrial fission and protein kinase R through the use of chemical inhibition in trophoblasts subjected to endotoxin lipopolysaccharide and double-stranded RNA analog polyinosinic:polycytidylic acid stress. (bvsalud.org)
  • Expressions of protein kinase R, dynamin-related protein 1, mitochondrial fission protein 1, and heat shock protein 60 were determined by applying lipopolysaccharide and polyinosinic:polycytidylic acid to BeWo trophoblast cells. (bvsalud.org)
  • Next, cells were treated with protein kinase R inhibitor 2-aminopurine and mitochondrial division inhibitor 1 to examine changes in progesterone levels and expression levels of proteins and mRNAs involved in progesterone biosynthesis. (bvsalud.org)
  • Lipopolysaccharide and polyinosinic:polycytidylic acid stimulation induced mitochondrial fission and activated protein kinase R but decreased heat shock protein 60 levels and progesterone synthesis. (bvsalud.org)
  • Chemical inhibition of mitochondrial fission elevated progesterone synthesis and protein and mRNA levels of genes involved in progesterone biosynthesis. (bvsalud.org)
  • Inhibition of protein kinase R with 2-aminopurine prevented lipopolysaccharide and polyinosinic:polycytidylic acid induced mitochondrial fission and increased progesterone biosynthesis. (bvsalud.org)
  • The study reveals that inhibiting mitochondrial fragmentation and reducing activity of stress kinase protein kinase R in syncytiotrophoblasts leads to an increase in progesterone synthesis when exposed to lipopolysaccharide and polyinosinic:polycytidylic acid. (bvsalud.org)
  • Mitochondrial fission is mediated by the large GTPase, dynamin-related protein 1 (Drp1) which, when activated, translocates to the outer mitochondrial membrane (OMM) where it interacts with binding proteins (Fis1, MFF, MiD49 and MiD51). (bvsalud.org)
  • We identify mitoguardin-2, a mitochondrial protein at contacts with the ER and/or lipid droplets (LDs), as a lipid transporter. (rupress.org)
  • The PTS1 signal peptide is about 12 amino acids long present at the C-terminus of the protein [13]. (5dok.net)
  • Phosphatidic Acid is a unique type of fat molecule that directly activates mTOR -- the signaling pathway that drives muscle protein synthesis in humans . (highdefinitionsupplements.ca)
  • Lipin 1 is a bifunctional protein that is a transcriptional regulator and has phosphatidic acid (PA) phosphohydrolase activity, which dephosphorylates PA to generate diacylglycerol. (bioblast.at)
  • These data suggest that loss of lipin 1 impairs cardiac functional reserve, likely due to effects on glycerolipid homeostasis, mitochondrial function, and protein kinase A signaling. (bioblast.at)
  • The phosphate group, when bound to other head molecules such as hydrogen, and ethanolamine, it's known as phosphatidic acid and phosphatidylethanolamine. (microbenotes.com)
  • The lipid precursor phosphatidylethanolamine (PTLM), through the action of N -acyltransferase (NAT) and of arachidonic acid (ARa), leads to the formation of N -arachidonoyl-phosphatidylethonolamine (NAPE), which, through the action of NAPE-phospholipase D (NAPE-PLD), forms N -Arachidonoylethanolamine (anandamide-AEA) and phosphatidic acid (PHa). (encyclopedia.pub)
  • The human gene AGK encodes the enzyme mitochondrial acylglycerol kinase. (wikipedia.org)
  • 2005) mapped this disease to DDHD1 (DDHD-domain-containing 1), which belongs to the intracellular phospholipase A1 gene family and encodes phosphatidic acid-preferring phospholipase A1 (PA-PLA1). (preventiongenetics.com)
  • The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. (huji.ac.il)
  • Cs-Lpin1 -/- mice exhibited diminished cardiac cardiolipin content and impaired mitochondrial respiration rates when provided with pyruvate or succinate as metabolic substrates. (bioblast.at)
  • Different studies have reported that cannabinoids can reduce oxidative stress at mitochondrial and cellular levels. (encyclopedia.pub)
  • The regulation of membrane fusion and fission generates a striking diversity of mitochondrial shapes, ranging from numerous small spheres in hepatocytes to long branched tubules in myotubes. (jhmi.edu)
  • Significant oxidative damage and increased mitochondrial membrane permeability constitute the point-of-no-return of programmed cell death pathways. (lifestylematrix.com)
  • Membrane lipid replacement (MLR) is best utilized in the form of an oral phospholipid supplement that emulates the composition of the mitochondrial lipids. (lifestylematrix.com)
  • By effectively replacing these membrane lipids, mitochondrial function is optimized, and energy production is restored to optimal levels using a safe and cost-effective intervention. (lifestylematrix.com)
  • Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). (smpdb.ca)
  • Surprisingly, the phospholipid fatty acids are of two types where one is saturated and the other unsaturated, which is responsible for membrane fluidity and flexibility of the phospholipid membrane. (microbenotes.com)
  • Here we show that primary myoblasts from lipin-1-deficient patients exhibit a dramatic decrease in LPIN1 expression and phosphatidic acid phosphatase 1 activity, and a significant accumulation of lipid droplets (LD). (nih.gov)
  • 6. Li M Y,Hong Y Y,Wang X M. Phospholipase D-and phosphatidic acid-mediated signaling in plants[J]. Biochimica et Biophysica Acta(BBA)-Molecular and Cell Biology of Lipids,2009,1791(9):927-935. (nefu.edu.cn)
  • Following cell activation, phosphatidic acid is released and functions as a second messenger in several signaling pathways. (preventiongenetics.com)
  • Using yeast as a model system, we have identified several components that mediate and regulate mitochondrial fusion. (jhmi.edu)
  • Lipins also act in the nucleus as transcriptional co-activators with peroxisome proliferator-activated receptor γ co-activator-1α (PGC-1α) and peroxisome proliferator-activated receptor α to regulate target genes involved in fatty acid oxidation. (aocs.org)
  • The functions of the lipins in co-regulating the effects of PGC-1α and PPARα and also acting as a PAP demonstrate the unique abilities of lipins to regulate both glycerolipid synthesis and fatty acid oxidation. (aocs.org)
  • Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. (uams.edu)
  • Nucleic Acids Res. (uams.edu)
  • Epicatechin is also known to stimulate mitochondrial biogenesis and nitric oxide (NO) production, encouraging greater blood flow and nutrient delivery. (highdefinitionsupplements.ca)
  • Special attention was paid to the up-regulated ACACB (acetyl-CoA carboxylase beta), a key enzyme in the fatty acid synthesis/oxidation balance. (nih.gov)
  • We found that ligand activation of PPARγ dramatically induced de novo lipid synthesis as well as fatty acid beta (β)-oxidation in lung cancer both in vitro and in vivo . (oncotarget.com)
  • The enzyme is involved in the more general pathway of fatty acid metabolism. (wikipedia.org)
  • In E. coli glycerophospholipid metabolism, The biosynthesis of CDP-diacylglycerol (CDP-DG) involves condensation of phosphatidic acid (PA) and cytidine triphosphate, with elimination of pyrophosphate, catalysed by the enzyme CDP-diacylglycerol synthase. (ymdb.ca)
  • The enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. (smpdb.ca)
  • Wikipedia) De novo biosynthesis of triglycerides is also known as the phosphatidic acid pathway, and it is mainly associated with the liver and adipose tissue. (smpdb.ca)
  • We demonstrated that overexpression of ACACB was associated with free fatty acid accumulation in patients' myoblasts whereas malonyl-carnitine (as a measure of malonyl-CoA) and CPT1 activity were in the normal range in basal conditions accordingly to the normal daily activity reported by the patients. (nih.gov)
  • Pathogenic variants in DDHD1 may cause mitochondrial dysfunctions that result from the accumulation of phosphatidic acid (Higgs et al. (preventiongenetics.com)
  • Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. (huji.ac.il)
  • Defects in this gene have been associated with mitochondrial DNA depletion syndrome 10. (wikipedia.org)
  • We support the concept that elevated glucose and fatty acids synergize in causing toxicity in islets and other organs, a process that may be instrumental in the pleiotropic defects associated with the metabolic syndrome and type 1 and type 2 diabetes. (diabetesjournals.org)
  • Therefore, it is not surprising that defects in mitochondrial fusion cause neurodegenerative disorders in humans, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. (jhmi.edu)
  • The integrity of mitochondrial membranes is critical to cell function and energy metabolism. (lifestylematrix.com)
  • ALA is a mitochondrial compound that works similarly to ALCAR involved in energy metabolism and the production of acetylcholine. (nuoptimal.com)
  • Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. (huji.ac.il)
  • A fluorescence-based process applying Magnesium Green, a Mg2+ -sensitive dye, was utilized to evaluate ATP/ADP exchange by way of mitochondrial adenine nucleotide translocase [271]. (nicotinic-receptor.com)
  • Acylglycerol kinase synthesizes phosphatidic and lysophosphatidic acids. (wikipedia.org)
  • Last, effect of 2-aminopurine on mitochondrial fission was determined by immunoblotting and quantitative PCR (qPCR). (bvsalud.org)
  • Here we review the role of mitochondrial dynamics in health and disease and discuss emerging concepts in the field, such as the role of central versus peripheral fission and the potential role of dynamin 2 (DNM2) as a fission mediator. (bvsalud.org)
  • In hyperproliferative diseases, such as pulmonary arterial hypertension and cancer, Drp1 and its binding partners are upregulated and activated, positing mitochondrial fission as an emerging therapeutic target. (bvsalud.org)
  • After reminding the reader of the basic concepts of mitochondrial genetics, she offers examples of disorders due to mutations in mitochondrial DNA and mutations in nuclear DNA. (medlink.com)
  • 1998). PA-PLA1 is involved in the maintenance of the Golgi and ER structure, and regulation of mitochondrial dynamics. (preventiongenetics.com)
  • PA-PLA1 is a lipase that catalyzes degradation of phosphatidic acid and attenuates cell activation (Higgs et al. (preventiongenetics.com)
  • Initially these disorders were named according to symptoms (later the cause was found to be mitochondrial dysfunction and more specifically maternally inherited mitochondrial DNA variations). (medlink.com)
  • 1 Many conditions lead to fatigue, but mitochondrial dysfunction is at the core. (lifestylematrix.com)
  • Phenylalanine is an amino acid that is a building block for the neurotransmitter dopamine. (nuoptimal.com)
  • Phenylalanine is an amino acid that has been shown to produce improved attention-span, mood, and motivation. (nuoptimal.com)
  • Extracellular Spermine Triggers a Rapid Intracellular Phosphatidic Acid Response in Arabidopsis, Involving PLDδ Activation and Stimulating Ion Flux. (uva.nl)
  • Local attraction of substrates and co-substrates enhances weak acid and base transmembrane transport, and principles in the attraction and facilitation of weak acid and base transport substrates, including monocarboxylates, ammonium, bicarbonate, and arsenite, plus protons as a co-substrate have been elucidated ( Epalle and Beitz 2022 ). (tcdb.org)
  • Few genes show differential expression with age in tissues (brain, liver and kidney) of naked mole rats and, contrary to other mammals and short-lived model animals, mitochondrial gene expression does not change with age 13 . (nature.com)
  • Figure: Phospholipid bilayer depicting hydrophobic tails of fatty acid chains and hydrophilic head of glycerol backbone, phosphate, and polar head group. (microbenotes.com)
  • Structurally, a phospholipid molecule comprises two fatty acid tails and a head with glycerol (3-carbon alcohol) and a phosphate molecule. (microbenotes.com)
  • One form of the disorder presented as vascular strokes, lactic acidosis, cardiomyopathy and cataracts, abnormal muscle cell histopathology and mitochondrial function. (wikipedia.org)
  • In addition to shape and number, mitochondrial fusion is critical for normal organelle function. (jhmi.edu)
  • Murata D, Yamada T, Tokuyama T, Arai K, Quirós PM, López-Otín C, Iijima M, Sesaki H. Mitochondrial Safeguard: a stress response that offsets extreme fusion and protects respiratory function via flickering-induced Oma1 activation. (jhmi.edu)
  • ALCAR improves mitochondrial function and increase levels of noradrenaline, associated with focus and alertness. (nuoptimal.com)
  • We then discuss how obesity leads to insulin resistance via a complex interplay among systemic fatty acid excess, microhypoxia in adipose tissue, ER stress, and inflammation. (jci.org)
  • Research indicates that phosphatidic acid supplementation enhances the anabolic (muscle building) effects of resistance-training programs. (highdefinitionsupplements.ca)
  • β-Cells possess inherent mechanisms to adapt to overnutrition and the prevailing concentrations of glucose, fatty acids, and other fuels to maintain glucose homeostasis. (diabetesjournals.org)
  • Both glucose and fatty acids may cause good/adaptive or evil/toxic actions on the β-cell, depending on their concentrations and the time during which they are elevated. (diabetesjournals.org)
  • We discuss here the emerging view that β-cell "glucotoxicity" is in part indirectly caused by "lipotoxicity," and that β-cell abnormalities will become particularly apparent when both glucose and circulating fatty acids are high. (diabetesjournals.org)
  • Moreover, mitochondrial fusion also regulates the release of cytochrome C during apoptosis. (jhmi.edu)
  • Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. (plos.org)
  • Mitochondrial disorders describe a broad range of disorders that have multiple genetic causes and variable symptoms and signs. (medlink.com)
  • A monoglyceride, more correctly known as a monoacylglycerol, is a glyceride consisting of one fatty acid chain covalently bonded to a glycerol molecule through an ester linkage. (hmdb.ca)
  • Monoacylglycerols are formed biochemically via release of a fatty acid from diacylglycerol by diacylglycerol lipase or hormone sensitive lipase. (hmdb.ca)
  • Through the action of diacylglycerol lipase (DAGL) and arachidonic acid (ARa) on 1,2-DAG, 2-AG is formed. (encyclopedia.pub)
  • In this review of what is probably the most heterogeneous group of human diseases (the mitochondrial diseases including encephalomyopathies), the author tries to offer the clinician a rational diagnostic framework. (medlink.com)
  • Mitochondrial structural changes were also examined by transmission electron microscopy. (bvsalud.org)