Photosynthetic capacity of the inflorescence is a major contributor to daily-C-gain and the responsiveness of growth to elevated CO2 in Arabidopsis thaliana with repressed expression of mitochondrial-pyruvate-dehydrogenase-kinase

2014 ◽  
Vol 107 ◽  
pp. 84-97 ◽  
Author(s):  
Evangelos D. Leonardos ◽  
Shezad A. Rauf ◽  
Sarathi M. Weraduwage ◽  
Elizabeth-France Marillia ◽  
David C. Taylor ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Elevated Co2 ◽  
Pyruvate Dehydrogenase ◽  
Photosynthetic Capacity ◽  
Pyruvate Dehydrogenase Kinase ◽  
Major Contributor

Pyruvate dehydrogenase kinase from Arabidopsis thaliana: a protein histidine kinase that phosphorylates serine residues

2000 ◽  
Vol 349 (1) ◽  
pp. 195-201 ◽  
Author(s):  
Jay J. THELEN ◽  
Jan A. MIERNYK ◽  
Douglas D. RANDALL
Keyword(s):  
Arabidopsis Thaliana ◽  
Pyruvate Dehydrogenase ◽  
Histidine Kinase ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Primary Amino Acid Sequence ◽  
N Terminus ◽  
Primary Amino

Pyruvate dehydrogenase kinase (PDK) is the primary regulator of flux through the mitochondrial pyruvate dehydrogenase complex (PDC). Although PDKs inactivate mitochondrial PDC by phosphorylating specific Ser residues, the primary amino acid sequence indicates that they are more closely related to prokaryotic His kinases than to eukaryotic Ser/Thr kinases. Unlike Ser/Thr kinases, His kinases use a conserved His residue for phosphotransfer to Asp residues. To understand these unique kinases better, a presumptive PDK from Arabidopsis thaliana was heterologously expressed and purified for this investigation. Purified, recombinant A. thaliana PDK could inactivate kinase-depleted maize mitochondrial PDC by phosphorylating Ser residues. Additionally, A. thaliana PDK was capable of autophosphorylating Ser residues near its N-terminus, although this reaction is not part of the phosphotransfer pathway. To elucidate the mechanism involved, we performed site-directed mutagenesis of the canonical His residue likely to be involved in phosphotransfer. When His-121 was mutated to Ala or Gln, Ser-autophosphorylation was decreased by 50% and transphosphorylation of PDC was decreased concomitantly. We postulate that either (1) His-121 is not the sole phosphotransfer His residue or (2) mutagenesis of His-121 exposes an additional otherwise cryptic phosphotransfer His residue. Thus His-121 is one residue involved in kinase function.

scholarly journals Histidine mutagenesis of Arabidopsis thaliana pyruvate dehydrogenase kinase

2002 ◽  
Vol 269 (10) ◽  
pp. 2601-2606 ◽  
Author(s):  
Alejandro Tovar-Mendez ◽  
Jan A. Miernyk ◽  
Douglas D. Randall
Keyword(s):  
Arabidopsis Thaliana ◽  
Pyruvate Dehydrogenase ◽  
Pyruvate Dehydrogenase Kinase

scholarly journals Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yeram Park ◽  
Deunsol Hwang ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Pyruvate Dehydrogenase ◽  
Hypoxic Condition ◽  
Open Circuit ◽  
Pyruvate Dehydrogenase Kinase ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

scholarly journals Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Jin ◽  
Eun-Yeong Kim ◽  
Tae-Wook Chung ◽  
Chang Woo Han ◽  
So Young Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cancer Drug ◽  
Potential Candidate ◽  
Mitochondrial Ros

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

scholarly journals Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 325
Author(s):  
Carolina Venturoli ◽  
Ilaria Piga ◽  
Matteo Curtarello ◽  
Martina Verza ◽  
Giovanni Esposito ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Metabolic Pathways ◽  
Negative Impact ◽  
Digital Pathology ◽  
Pyruvate Dehydrogenase Kinase ◽  
Ovarian Cancer Cells ◽  
Pyruvate Dehydrogenase Kinase 1

Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways—comprising both oxidative phosphorylation and glycolysis—in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.

scholarly journals Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

2021 ◽  
Vol 22 (2) ◽  
pp. 764
Author(s):  
Russel J. Reiter ◽  
Ramaswamy Sharma ◽  
Sergio Rosales-Corral
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Warburg Effect ◽  
Coenzyme A ◽  
Aerobic Glycolysis ◽  
Pyruvate Dehydrogenase Complex ◽  
Pyruvate Dehydrogenase Kinase ◽  
Metabolic Phenotype ◽  
Common Denominator ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, is transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, pyruvate transport into the mitochondria is blocked due to the inhibition of PDC by pyruvate dehydrogenase kinase. This altered metabolism is referred to as aerobic glycolysis (Warburg effect) and is common in solid tumors and in other pathological cells. Switching from mitochondrial oxidative phosphorylation to aerobic glycolysis provides diseased cells with advantages because of the rapid production of ATP and the activation of pentose phosphate pathway (PPP) which provides nucleotides required for elevated cellular metabolism. Molecules, called glycolytics, inhibit aerobic glycolysis and convert cells to a healthier phenotype. Glycolytics often function by inhibiting hypoxia-inducible factor-1α leading to PDC disinhibition allowing for intramitochondrial conversion of pyruvate into acetyl coenzyme A. Melatonin is a glycolytic which converts diseased cells to the healthier phenotype. Herein we propose that melatonin’s function as a glycolytic explains its actions in inhibiting a variety of diseases. Thus, the common denominator is melatonin’s action in switching the metabolic phenotype of cells.

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