The Experts below are selected from a list of 12237 Experts worldwide ranked by ideXlab platform
David Clarke - One of the best experts on this subject based on the ideXlab platform.
-
A Metabolic Switch is involved in lifestyle decisions in Photorhabdus luminescens
Molecular microbiology, 2010Co-Authors: Lea Lango, David ClarkeAbstract:Photorhabdus luminescens is a species of Gram-negative bacteria that is pathogenic to insects while also maintaining a mutualistic association with nematodes from the family Heterorhabditis. P. luminescens elaborates an extensive secondary metabolism during the post-exponential phase of growth that includes the production of an antibiotic called 3-5-dihydroxy-4-isopropylstilbene (ST), an anthraquinone pigment (AQ) and bioluminescence. In this study we identified a mutant that was unable to produce ST, AQ and light. This mutation was found to be in the mdh gene, encoding malate dehydrogenase, a key enzyme in the tricarboxylic acid (TCA) cycle. Interestingly the mdh mutant was unaffected in virulence but was unable to support nematode growth and development in vivo or in vitro. This clearly establishes that secondary metabolism in P. luminescens is required for the mutualistic interaction with the nematode. Furthermore, the construction of mutations in key genes in other central Metabolic pathways confirmed the critical role for the TCA cycle in both secondary metabolism and mutualism, but not in virulence. Therefore, we conclude that the TCA cycle is required for the transition of P. luminescens from pathogen to mutualist implicating the involvement of a Metabolic Switch in the regulation of lifestyle decisions in this bacterium.
-
A Metabolic Switch is involved in life-style decisions in Photorhabdus luminescens
Molecular Microbiology, 2010Co-Authors: Lea Lango, David ClarkeAbstract:Photorhabdus luminescens is a species of Gram negative bacteria that is pathogenic to insects whilst also maintaining a mutualistic association with nematodes from the family Heterorhabditis. P. luminescens elaborates an extensive secondary metabolism during the post-exponential phase of growth that includes the production of an antibiotic called 3-5-dihydroxy-4-isopropylstilbebe (ST), an anthraquinone pigment (AQ) and bioluminescence. In this study we identified a mutant that was unable to produce ST, AQ and light. This mutation was found to be in the mdh gene, encoding malate dehydrogenase, a key enzyme in the TCA cycle. Interestingly the mdh mutant was unaffected in virulence but was unable to support nematode growth and development in vivo or in vitro. This clearly establishes that secondary metabolism in P. luminescens is required for the mutualistic interaction with the nematode. Furthermore the construction of mutations in key genes in other central Metabolic pathways confirmed the critical role for the TCA cycle in both secondary metabolism and mutualism, but not in virulence. Therefore we conclude that the TCA cycle is required for the transition of P. luminescens from pathogen to mutualist implicating the involvement of a Metabolic Switch in the regulation of life-style decisions in this bacterium.
Urs Jenal - One of the best experts on this subject based on the ideXlab platform.
-
Reciprocal growth control by competitive binding of nucleotide second messengers to a Metabolic Switch in Caulobacter crescentus
Nature Microbiology, 2020Co-Authors: Viktoriya Shyp, Badri Nath Dubey, Raphael Böhm, Johannes Hartl, Jutta Nesper, Julia A. Vorholt, Sebastian Hiller, Tilman Schirmer, Urs JenalAbstract:Bacteria use small signalling molecules such as (p)ppGpp or c-di-GMP to tune their physiology in response to environmental changes. It remains unclear whether these regulatory networks operate independently or whether they interact to optimize bacterial growth and survival. We report that (p)ppGpp and c-di-GMP reciprocally regulate the growth of Caulobacter crescentus by converging on a single small-molecule-binding protein, SmbA. While c-di-GMP binding inhibits SmbA, (p)ppGpp competes for the same binding site to sustain SmbA activity. We demonstrate that (p)ppGpp specifically promotes Caulobacter growth on glucose, whereas c-di-GMP inhibits glucose consumption. We find that SmbA contributes to this Metabolic Switch and promotes growth on glucose by quenching the associated redox stress. The identification of an effector protein that acts as a central regulatory hub for two global second messengers opens up future studies on specific crosstalk between small-molecule-based regulatory networks. Crosstalk between small-molecule regulated networks controls growth in Caulobacter crescentus .
-
Reciprocal growth control by competitive binding of nucleotide second messengers to a Metabolic Switch in Caulobacter crescentus.
Nature microbiology, 2020Co-Authors: Viktoriya Shyp, Badri Nath Dubey, Raphael Böhm, Johannes Hartl, Jutta Nesper, Julia A. Vorholt, Sebastian Hiller, Tilman Schirmer, Urs JenalAbstract:Bacteria use small signalling molecules such as (p)ppGpp or c-di-GMP to tune their physiology in response to environmental changes. It remains unclear whether these regulatory networks operate independently or whether they interact to optimize bacterial growth and survival. We report that (p)ppGpp and c-di-GMP reciprocally regulate the growth of Caulobacter crescentus by converging on a single small-molecule-binding protein, SmbA. While c-di-GMP binding inhibits SmbA, (p)ppGpp competes for the same binding site to sustain SmbA activity. We demonstrate that (p)ppGpp specifically promotes Caulobacter growth on glucose, whereas c-di-GMP inhibits glucose consumption. We find that SmbA contributes to this Metabolic Switch and promotes growth on glucose by quenching the associated redox stress. The identification of an effector protein that acts as a central regulatory hub for two global second messengers opens up future studies on specific crosstalk between small-molecule-based regulatory networks.
Claire Pecqueur - One of the best experts on this subject based on the ideXlab platform.
-
uncoupling protein 2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis derived pyruvate utilization
The FASEB Journal, 2008Co-Authors: Claire Pecqueur, Thi Bui, C Gelly, Julie Hauchard, Celine Barbot, Frederic Bouillaud, Daniel Ricquier, Bruno Miroux, Craig B ThompsonAbstract:Uncoupling protein-2 (UCP2) belongs to the mitochondrial carrier family and has been thought to be involved in suppressing mitochondrial ROS production through uncoupling mitochondrial respiration from ATP synthesis. However, we show here that loss of function of UCP2 does not result in a significant increase in ROS production or an increased propensity for cells to undergo senescence in culture. Instead, Ucp2−/− cells display enhanced proliferation associated with a Metabolic Switch from fatty acid oxidation to glucose metabolism. This Metabolic Switch requires the unrestricted availability of glucose, and Ucp2−/− cells more readily activate autophagy than wild-type cells when deprived of glucose. Altogether, these results suggest that UCP2 promotes mitochondrial fatty acid oxidation while limiting mitochondrial catabolism of pyruvate. The persistence of fatty acid catabolism in Ucp2+/+ cells during a proliferative response correlates with reduced cell proliferation and enhances resistance to glucose sta...
-
Uncoupling protein-2 controls proliferation by promoting fatty acid oxidation and limiting glycolysis-derived pyruvate utilization
FASEB Journal, 2008Co-Authors: Claire Pecqueur, Thi Bui, C Gelly, Julie Hauchard, Celine Barbot, Frederic Bouillaud, Daniel Ricquier, Bruno Miroux, Craig ThompsonAbstract:Uncoupling protein-2 (UCP2) belongs to the mitochondrial carrier family and has been thought to be involved in suppressing mitochondrial ROS production through uncoupling mitochondrial respiration from ATP synthesis. However, we show here that loss of function of UCP2 does not result in a significant increase in ROS production or an increased propensity for cells to undergo senescence in culture. Instead, Ucp2-/- cells display enhanced proliferation associated with a Metabolic Switch from fatty acid oxidation to glucose metabolism. This Metabolic Switch requires the unrestricted availability of glucose, and Ucp2-/- cells more readily activate autophagy than wild-type cells when deprived of glucose. Altogether, these results suggest that UCP2 promotes mitochondrial fatty acid oxidation while limiting mitochondrial catabolism of pyruvate. The persistence of fatty acid catabolism in Ucp2-/- cells during a proliferative response correlates with reduced cell proliferation and enhances resistance to glucose starvation-induced autophagy.
Chi V Dang - One of the best experts on this subject based on the ideXlab platform.
-
hif 1 mediated expression of pyruvate dehydrogenase kinase a Metabolic Switch required for cellular adaptation to hypoxia
Cell Metabolism, 2006Co-Authors: Irina Tchernyshyov, Gregg L Semenza, Chi V DangAbstract:Summary Activation of glycolytic genes by HIF-1 is considered critical for Metabolic adaptation to hypoxia through increased conversion of glucose to pyruvate and subsequently to lactate. We found that HIF-1 also actively suppresses metabolism through the tricarboxylic acid cycle (TCA) by directly trans -activating the gene encoding pyruvate dehydrogenase kinase 1 (PDK1). PDK1 inactivates the TCA cycle enzyme, pyruvate dehydrogenase (PDH), which converts pyruvate to acetyl-CoA. Forced PDK1 expression in hypoxic HIF-1α null cells increases ATP levels, attenuates hypoxic ROS generation, and rescues these cells from hypoxia-induced apoptosis. These studies reveal a hypoxia-induced Metabolic Switch that shunts glucose metabolites from the mitochondria to glycolysis to maintain ATP production and to prevent toxic ROS production.
Shaw Jenq Tsai - One of the best experts on this subject based on the ideXlab platform.
-
induction of pyruvate dehydrogenase kinase 3 by hypoxia inducible factor 1 promotes Metabolic Switch and drug resistance
Journal of Biological Chemistry, 2008Co-Authors: Chun Wun Lu, Kofan Chen, Shaw Jenq TsaiAbstract:The Switch of cellular metabolism from mitochondrial respiration to glycolysis is the hallmark of cancer cells and associated with tumor malignancy. However, the mechanism of this Metabolic Switch remains largely unknown. Herein, we reported that hypoxia-inducible factor-1 (HIF-1) induced pyruvate dehydrogenase kinase-3 (PDK3) expression leading to inhibition of mitochondrial respiration. Promoter activity assay, small interference RNA knockdown assay, and chromatin immunoprecipitation assay demonstrated that hypoxia-induced PDK3 gene activity was regulated by HIF-1 at the transcriptional level. Forced expression of PDK3 in cancer cells resulted in increased lactic acid accumulation and drugs resistance, whereas knocking down PDK3 inhibited hypoxia-induced cytoplasmic glycolysis and cell survival. These data demonstrated that increased PDK3 expression due to elevated HIF-1α in cancer cells may play critical roles in Metabolic Switch during cancer progression and chemoresistance in cancer therapy.