Abnormal early folliculogenesis due to impeded pyruvate metabolism in mouse oocytes

2021 ◽  
Author(s):  
Keiko Tanaka ◽  
Yohei Hayashi ◽  
Asuka Takehara ◽  
Yumi Ito-Matsuoka ◽  
Masahito Tachibana ◽  
...  
Keyword(s):  
Germ Cells ◽  
Energy Production ◽  
Tca Cycle ◽  
Pyruvate Metabolism ◽  
Organ Cultures ◽  
Characteristic Energy ◽  
Fetal Mouse ◽  
The Tca Cycle ◽  
Intermediate Metabolites ◽  
Possible Cause

Abstract Fetal ovarian germ cells show characteristic energy metabolism status, such as enhanced mitochondrial metabolism as well as glycolysis, but their roles in early folliculogenesis are unclear. We show here that inhibition of pyruvate uptake to mitochondria by UK5099 in organ cultures of fetal mouse ovaries resulted in repressed early folliculogenesis without affecting energy production, survival of oocytes, or meiosis. In addition, the abnormal folliculogenesis by UK5099 was partially rescued by α-ketoglutarate and succinate, intermediate metabolites in the TCA cycle, suggesting the importance of those metabolites. The expression of TGFβ-related genes Gdf9 and Bmp15 in ovarian germ cells, which are crucial for folliculogenesis, was downregulated by UK5099, and the addition of recombinant GDF9 partially rescued the abnormal folliculogenesis induced by UK5099. We also found that early folliculogenesis was similarly repressed, as in the culture, in the ovaries of a germ cell-specific knockout of Mpc2, which encodes a mitochondria pyruvate carrier that is targeted by UK5099. These results suggest that insufficient Gdf9 expression induced by abnormal pyruvate metabolism in oocytes results in early follicular dysgenesis, which is a possible cause of defective folliculogenesis in humans.

scholarly journals rre37Overexpression Alters Gene Expression Related to the Tricarboxylic Acid Cycle and Pyruvate Metabolism inSynechocystissp. PCC 6803

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hiroko Iijima ◽  
Atsuko Watanabe ◽  
Junko Takanobu ◽  
Masami Yokota Hirai ◽  
Takashi Osanai
Keyword(s):  
Gene Expression ◽  
Response Regulator ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Nitrogen Depletion ◽  
Pyruvate Metabolism ◽  
Unicellular Cyanobacterium ◽  
The Tca Cycle ◽  
In The Wild

The tricarboxylic acid (TCA) cycle and pyruvate metabolism of cyanobacteria are unique and important from the perspectives of biology and biotechnology research. Rre37, a response regulator induced by nitrogen depletion, activates gene expression related to sugar catabolism. Our previous microarray analysis has suggested that Rre37 controls the transcription of genes involved in sugar catabolism, pyruvate metabolism, and the TCA cycle. In this study, quantitative real-time PCR was used to measure the transcript levels of 12 TCA cycle genes and 13 pyruvate metabolism genes. The transcripts of 6 genes (acnB,icd,ppc,pyk1,me, andpta) increased after 4 h of nitrogen depletion in the wild-type GT strain but the induction was abolished byrre37overexpression. The repression of gene expression offumC, ddh, andackAcaused by nitrogen depletion was abolished byrre37overexpression. The expression ofmewas differently affected byrre37overexpression, compared to the other 24 genes. These results indicate that Rre37 differently controls the genes of the TCA cycle and pyruvate metabolism, implying the key reaction of the primary in this unicellular cyanobacterium.

scholarly journals Exposure of Clinical MRSA Heterogeneous Strains to β-Lactams Redirects Metabolism to Optimize Energy Production through the TCA Cycle

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e71025 ◽  
Author(s):  
Mignon A. Keaton ◽  
Roberto R. Rosato ◽  
Konrad B. Plata ◽  
Christopher R. Singh ◽  
Adriana E. Rosato
Keyword(s):  
Energy Production ◽  
Tca Cycle ◽  
The Tca Cycle

Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle

2005 ◽  
Vol 288 (2) ◽  
pp. E327-E334 ◽  
Author(s):  
Paul A. Roberts ◽  
Susan J. G. Loxham ◽  
Simon M. Poucher ◽  
Dumitru Constantin-Teodosiu ◽  
Paul L. Greenhaff
Keyword(s):  
Skeletal Muscle ◽  
Energy Production ◽  
Pyruvate Dehydrogenase Complex ◽  
Tca Cycle ◽  
Treated Group ◽  
Acetyl Coa ◽  
Tension Development ◽  
The Tca Cycle ◽  
Work Transition ◽  
Acetyl Group

We examined the effects of increasing acetylcarnitine and acetyl-CoA availability at rest, independent of pyruvate dehydrogenase complex (PDC) activation, on energy production and tension development during the rest-to-work transition in canine skeletal muscle. We aimed to elucidate whether the lag in PDC-derived acetyl-CoA delivery toward the TCA cycle at the onset of exercise can be overcome by increasing acetyl group availability independently of PDC activation or is intimately dependent on PDC-derived acetyl-CoA. Gracilis muscle pretreated with saline or sodium acetate (360 mg/kg body mass) (both n = 6) was sampled repeatedly during 5 min of ischemic contraction. Acetate increased acetylcarnitine and acetyl-CoA availability (both P < 0.01) above control at rest and throughout contraction ( P < 0.05), independently of differences in resting PDC activation between treatments. Acetate reduced oxygen-independent ATP resynthesis ∼40% ( P < 0.05) during the first minute of contraction. No difference in oxygen-independent ATP resynthesis existed between treatments from 1 to 3 min of contraction; however, energy production via this route increased ∼25% ( P < 0.05) above control in the acetate-treated group during the final 2 min of contraction. Tension development was ∼20% greater after 5-min contraction after acetate treatment than in control ( P < 0.05). In conclusion, at the immediate onset of contraction, when PDC was largely inactive, increasing cellular acetyl group availability overcame inertia in mitochondrial ATP regeneration. However, after the first minute, when PDC was near maximally activated in both groups, it appears that PDC-derived acetyl-CoA, rather than increased cellular acetyl group availability per se, dictated mitochondrial ATP resynthesis.

scholarly journals Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1259
Author(s):  
Alexis Paulina Jiménez-Uribe ◽  
Estefani Yaquelin Hernández-Cruz ◽  
Karla Jaqueline Ramírez-Magaña ◽  
José Pedraza-Chaverri
Keyword(s):  
Energy Production ◽  
Calcium Influx ◽  
Kidney Diseases ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Intrinsic Pathway ◽  
Cytochrome C Release ◽  
Primary Function ◽  
The Tca Cycle

Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.

Liquid-liquid extraction of succinate using a dicopper cryptate

2020 ◽  
Author(s):  
Riccardo Mobili ◽  
Sonia La Cognata ◽  
Francesca Merlo ◽  
Andrea Speltini ◽  
Massimo Boiocchi ◽  
...  
Keyword(s):  
Aqueous Phase ◽  
Visible Spectrum ◽  
Tca Cycle ◽  
Residual Concentration ◽  
Waste Products ◽  
Liquid Liquid Extraction ◽  
The Tca Cycle ◽  
Quantitative Extraction ◽  
Uv Visible

<div> <p>The extraction of the succinate dianion from a neutral aqueous solution into dichloromethane is obtained using a lipophilic cage-like dicopper(II) complex as the extractant. The quantitative extraction exploits the high affinity of the succinate anion for the cavity of the azacryptate. The anion is effectively transferred from the aqueous phase, buffered at pH 7 with HEPES, into dichloromethane. A 1:1 extractant:anion adduct is obtained. Extraction can be easily monitored by following changes in the UV-visible spectrum of the dicopper complex in dichloromethane, and by measuring the residual concentration of succinate in the aqueous phase by HPLC−UV. Considering i) the relevance of polycarboxylates in biochemistry, as e.g. normal intermediates of the TCA cycle, ii) the relevance of dicarboxylates in the environmental field, as e.g. waste products of industrial processes, and iii) the recently discovered role of succinate and other dicarboxylates in pathophysiological processes including cancer, our results open new perspectives for research in all contexts where selective recognition, trapping and extraction of polycarboxylates is required. </p> </div>

scholarly journals Mitochondrial Mistranslation in Brain Provokes a Metabolic Response Which Mitigates the Age-Associated Decline in Mitochondrial Gene Expression

2021 ◽  
Vol 22 (5) ◽  
pp. 2746
Author(s):  
Dimitri Shcherbakov ◽  
Reda Juskeviciene ◽  
Adrián Cortés Sanchón ◽  
Margarita Brilkova ◽  
Hubert Rehrauer ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Response ◽  
Mitochondrial Gene ◽  
Tca Cycle ◽  
Brain Mitochondria ◽  
Mitochondrial Gene Expression ◽  
Rna Seq ◽  
The Tca Cycle ◽  
Neurological Phenotype

Mitochondrial misreading, conferred by mutation V338Y in mitoribosomal protein Mrps5, in-vivo is associated with a subtle neurological phenotype. Brain mitochondria of homozygous knock-in mutant Mrps5V338Y/V338Y mice show decreased oxygen consumption and reduced ATP levels. Using a combination of unbiased RNA-Seq with untargeted metabolomics, we here demonstrate a concerted response, which alleviates the impaired functionality of OXPHOS complexes in Mrps5 mutant mice. This concerted response mitigates the age-associated decline in mitochondrial gene expression and compensates for impaired respiration by transcriptional upregulation of OXPHOS components together with anaplerotic replenishment of the TCA cycle (pyruvate, 2-ketoglutarate).

scholarly journals Metabolomics of aging in primary fibroblasts from small and large breed dogs

GeroScience ◽  
2021 ◽  
Author(s):  
Paul S. Brookes ◽  
Ana Gabriela Jimenez
Keyword(s):  
Aging Process ◽  
Tca Cycle ◽  
Therapeutic Strategies ◽  
Targeted Metabolomics ◽  
The Tca Cycle ◽  
Age Dependent ◽  
Primary Fibroblasts ◽  
Aging Rates ◽  
Underlying Mechanisms ◽  
Coenzyme A Biosynthesis

AbstractAmong several animal groups (eutherian mammals, birds, reptiles), lifespan positively correlates with body mass over several orders of magnitude. Contradicting this pattern are domesticated dogs, with small dog breeds exhibiting significantly longer lifespans than large dog breeds. The underlying mechanisms of differing aging rates across body masses are unclear, but it is generally agreed that metabolism is a significant regulator of the aging process. Herein, we performed a targeted metabolomics analysis on primary fibroblasts isolated from small and large breed young and old dogs. Regardless of size, older dogs exhibited lower glutathione and ATP, consistent with a role for oxidative stress and bioenergetic decline in aging. Furthermore, several size-specific metabolic patterns were observed with aging, including the following: (i) An apparent defect in the lower half of glycolysis in large old dogs at the level of pyruvate kinase. (ii) Increased glutamine anaplerosis into the TCA cycle in large old dogs. (iii) A potential defect in coenzyme A biosynthesis in large old dogs. (iv) Low nucleotide levels in small young dogs that corrected with age. (v) An age-dependent increase in carnitine in small dogs that was absent in large dogs. Overall, these data support the hypothesis that alterations in metabolism may underlie the different lifespans of small vs. large breed dogs, and further work in this area may afford potential therapeutic strategies to improve the lifespan of large dogs.

scholarly journals The Metabolic Fates of Pyruvate in Normal and Neoplastic Cells

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 762
Author(s):  
Edward V. Prochownik ◽  
Huabo Wang
Keyword(s):  
Metabolic Pathways ◽  
Redox State ◽  
Pyruvate Dehydrogenase Complex ◽  
Tca Cycle ◽  
Vascular Supply ◽  
Extrinsic Factors ◽  
The Tca Cycle ◽  
Initial Substrate ◽  
Numerous Cell ◽  
Bio Synthesis

Pyruvate occupies a central metabolic node by virtue of its position at the crossroads of glycolysis and the tricarboxylic acid (TCA) cycle and its production and fate being governed by numerous cell-intrinsic and extrinsic factors. The former includes the cell’s type, redox state, ATP content, metabolic requirements and the activities of other metabolic pathways. The latter include the extracellular oxygen concentration, pH and nutrient levels, which are in turn governed by the vascular supply. Within this context, we discuss the six pathways that influence pyruvate content and utilization: 1. The lactate dehydrogenase pathway that either converts excess pyruvate to lactate or that regenerates pyruvate from lactate for use as a fuel or biosynthetic substrate; 2. The alanine pathway that generates alanine and other amino acids; 3. The pyruvate dehydrogenase complex pathway that provides acetyl-CoA, the TCA cycle’s initial substrate; 4. The pyruvate carboxylase reaction that anaplerotically supplies oxaloacetate; 5. The malic enzyme pathway that also links glycolysis and the TCA cycle and generates NADPH to support lipid bio-synthesis; and 6. The acetate bio-synthetic pathway that converts pyruvate directly to acetate. The review discusses the mechanisms controlling these pathways, how they cross-talk and how they cooperate and are regulated to maximize growth and achieve metabolic and energetic harmony.

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