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Metabolic efficiency underpins performance trade-offs in growth of Arabidopsis thaliana
Resources are finite for living organisms; therefore, compromises are required when partitioning resources to different tasks. Here, the authors use the Pareto concept to show how a trade-off is achieved in terms of the performance and metabolic efficiency in a panel of 97 Arabidopsis thalianaaccessions.
- Sabrina Kleessen
- , Roosa Laitinen
- & Zoran Nikoloski
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Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s–PPARα axis signalling
The IRE1α-XBP1 signalling pathway is part of the ER stress response but has also been linked to glucose and lipid metabolism. Here the authors show that IRE1α in the liver acts as a nutrient-sensor, regulating the metabolic adaptation to fasting and a ketogenic diet by inducing PPARα expression.
- Mengle Shao
- , Bo Shan
- & Yong Liu
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Ablation of TrkB signalling in CCK neurons results in hypercortisolism and obesity
Glucocorticoid levels in the body are controlled by an intricate feedback system acting on the hypothalamus. Here the authors provide molecular insight into this process, identifying TrkB signalling in cholecystokinin-GABAergic neurons as a key component of hypothalamic glucocorticoid signalling.
- Mirjam Geibel
- , Sylvia Badurek
- & Liliana Minichiello
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Genome-wide RNAi ionomics screen reveals new genes and regulation of human trace element metabolism
The composition of trace elements in human cells (the ionome) is an important component of metabolism. Here, the authors carry out a high-throughput, genome-wide analysis of the human ionome and identify cellular regulators of important trace elements such as selenium, copper and iron.
- Mikalai Malinouski
- , Nesrin M. Hasan
- & Vadim N. Gladyshev
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Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction
The milk-ejection reflex in mammals requires the coordinated bursting of oxytocin neurons in the hypothalamus. Here, Israel et al.show that the rhythmic bursting behaviour displayed by these neurons is active in both male and female neonatal rats, but is inactivated in males after the first week of life.
- Jean-Marc Israel
- , Jean-Marie Cabelguen
- & Philippe Ciofi
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| Open Access
Critical roles of nardilysin in the maintenance of body temperature homoeostasis
The precise regulation of mammalian body temperature is important for survival. Here the authors show that the peptidase nardilysin represses the transcription factor PGC-1α, and identify nardilysin as a regulator of basal body temperature, cold-induced thermogenesis and body insulation.
- Yoshinori Hiraoka
- , Tatsuhiko Matsuoka
- & Eiichiro Nishi
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Global metabolic network reorganization by adaptive mutations allows fast growth of Escherichia coli on glycerol
Organisms can adapt to environmental change but how this affects metabolism is unclear. Here, the authors provide a detailed analysis of the effects of individual adaptive mutations on the metabolic network in E. coli, and find evidence of metabolic reprogramming during laboratory evolution on glycerol.
- Kian-Kai Cheng
- , Baek-Seok Lee
- & Martin Robert
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| Open Access
Hypothalamic inhibition of socio-sexual behaviour by increasing neuroestrogen synthesis
The conversion of testosterone into oestrogen in the brain is implicated in male aggressive behaviour. Ubuka et al.show that gonadotropin-inhibitory hormone inhibits male aggression by increasing oestrogen synthesis in the brain beyond its optimum concentration for the expression of aggressive behaviour.
- Takayoshi Ubuka
- , Shogo Haraguchi
- & Kazuyoshi Tsutsui
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Mitochondrial reactive oxygen species regulate the strength of inhibitory GABA-mediated synaptic transmission
Cellular energy metabolism is essential for sustaining neuronal signalling in the brain. Acardi et al.show that mitochondrial reactive oxygen species, which are by-products of cellular metabolism, selectively strengthen inhibitory transmission by recruiting a subpopulation of GABAA receptors.
- Michael V. Accardi
- , Bryan A. Daniels
- & Derek Bowie
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Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease
Alterations in hepatocyte metabolism can lead to disorders such as non-alcoholic steatohepatitis (NASH). Here the authors create a comprehensive model of hepatocyte metabolism and use it to identify metabolic pathways altered in disease, revealing that serine levels are reduced in patients with NASH.
- Adil Mardinoglu
- , Rasmus Agren
- & Jens Nielsen
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Predicting network functions with nested patterns
Identifying functionally important features of complex biological networks is computationally challenging. Ganter et al.develop a probabilistic framework that uses recurrent metabolite patterns to predict the properties and existence of reactions within a genome-scale metabolic network.
- Mathias Ganter
- , Hans-Michael Kaltenbach
- & Jörg Stelling
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| Open Access
A failure in energy metabolism and antioxidant uptake precede symptoms of Huntington’s disease in mice
Defective ascorbic acid flux is a sign of metabolic failure associated with Huntington’s disease. Here, Acuña et al.show that reduction in ascorbic acid flux from astrocytes precedes the symptoms of Huntington’s disease in mice and impairs ascorbic acid uptake in neurons.
- Aníbal I. Acuña
- , Magdalena Esparza
- & Maite A. Castro
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Essential regulation of cell bioenergetics in Trypanosoma brucei by the mitochondrial calcium uniporter
The mitochondrial calcium uniporter supports oxidative phosphorylation in mammals; however, it is also present in blood-stage trypanosomes, which lack a functional respiratory chain. Huang et al. show that the mitochondrial calcium uniporter is essential for blood-stage survival and metabolism in Trypanosoma brucei.
- Guozhong Huang
- , Anibal E. Vercesi
- & Roberto Docampo
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Highly efficient methane biocatalysis revealed in a methanotrophic bacterium
Methane is a promising renewable carbon source for chemical synthesis, yet methane bio-gas is currently underutilised as a feedstock. Here the authors examine the metabolic processes of methanotrophic bacteria to assess their use for conversion of methane to value-added chemical products.
- M. G. Kalyuzhnaya
- , S. Yang
- & M. E. Lidstrom
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| Open Access
A truncated Wnt7a retains full biological activity in skeletal muscle
Wnt7a regulates various aspects of skeletal muscle function. Here, the authors show that a truncated Wnt7a protein lacking the palmitoylation domain retains its biological activity in skeletal muscle, suggesting that simplified Wnt7a proteins may be viable as Wnt-based therapeutics.
- Julia von Maltzahn
- , Radoslav Zinoviev
- & Michael A. Rudnicki
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Model-based identification of drug targets that revert disrupted metabolism and its application to ageing
Systems biology is considered a promising tool for the identification of new drug targets. Here Yizhak and colleagues present an algorithm to analyse gene expression data and identify potential drug targets that would shift cellular metabolism from a given disease state to that of a healthier state.
- Keren Yizhak
- , Orshay Gabay
- & Eytan Ruppin
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Switch of glycolysis to gluconeogenesis by dexamethasone for treatment of hepatocarcinoma
Hepatocytes use gluconeogenesis to produce glucose, but whether this process is altered in hepatocellular carcinoma (HCC) is unclear. Here, the loss of gluconeogenesis in HCC and altered glucocorticoid regulation is demonstrated and glucocorticoid treatment is shown to reduce tumour burden.
- Ruihua Ma
- , Wanguang Zhang
- & Bo Huang
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Human copper chaperone for superoxide dismutase 1 mediates its own oxidation-dependent import into mitochondria
The accumulation of superoxide in mitochondria is counteracted by superoxide dismutase 1 and its activating chaperone CCS1. Suzuki et al.show that in human cells, mature CCS1 itself mediates CCS1 import and helps to oxidize CCS1 and SOD1 in the mitochondrial intermembrane space.
- Yutaka Suzuki
- , Muna Ali
- & Jan Riemer
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| Open Access
Glycogen shortage during fasting triggers liver–brain–adipose neurocircuitry to facilitate fat utilization
During fasting, animals shift their energy source from carbohydrates to triglycerides. Here, Izumida et al. report that glycogen shortage in the liver activates a liver–brain–adipose-tissue neurocircuit that signals the switch in fuel source from liver glycogen to triglycerides in fat cells.
- Yoshihiko Izumida
- , Naoya Yahagi
- & Hitoshi Shimano
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Reductive glutamine metabolism is a function of the α-ketoglutarate to citrate ratio in cells
Reductive glutamine metabolism supports cell proliferation under stress conditions such as hypoxia. Here Fendtet al.report that the ratio between the two metabolites α-ketoglutarate and citrate determines whether glutamine is metabolized oxidatively or reductively.
- Sarah-Maria Fendt
- , Eric L. Bell
- & Gregory Stephanopoulos
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| Open Access
Brown fat in a protoendothermic mammal fuels eutherian evolution
Endothermy facilitated mammalian species radiation, but the events leading to sustained thermogenesis are not clear. Here, the authors report functional brown adipose tissue in a protoendothermic mammal, linking nonshivering thermogenesis directly to the roots of eutherian endothermic evolution.
- Rebecca Oelkrug
- , Nadja Goetze
- & Carola W. Meyer
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A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle
Interactions between mitochondrial respiratory chain complexes control electron transfer and oxidative phosphorylation. Here, the authors find that COX7RP regulates supercomplex assembly, and show that decreasing or increasing COX7RP expression, respectively, reduces and enhances muscular performance in mice.
- Kazuhiro Ikeda
- , Sachiko Shiba
- & Satoshi Inoue
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Large fibre size in skeletal muscle is metabolically advantageous
Energy demand in muscle is largely due to maintaining the membrane potential of muscle fibres. Jimenez et al.study the metabolic cost of maintaining the membrane potential of muscle fibres across different species of crustaceans and fishes, and find that larger fibres are metabolically cheaper to maintain.
- Ana Gabriela Jimenez
- , Richard M. Dillaman
- & Stephen T. Kinsey
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A common functional promoter variant links CNR1 gene expression to HDL cholesterol level
Haplotypes in CNR1, the gene encoding the cannabinoid receptor CB1, are known to influence HDL cholesterol levels. Here Feng and colleagues identify rs806371 as a novel regulatory element reducing CNR1 gene expression and as the causal allele driving the association between CNR1 and HDL cholesterol levels in humans.
- Q. Feng
- , K.C. Vickers
- & R.A. Wilke
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| Open Access
The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms
The murine G protein-coupled receptor 83 (Gpr83) is expressed widely in the brain, but its physiological role is largely unknown. Here Müller et al.show that Gpr83 regulates systemic energy metabolism in part by modulating ghrelin signalling in the arcuate nucleus of the hypothalamus.
- Timo D. Müller
- , Anne Müller
- & Matthias H. Tschöp
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| Open Access
The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43
The gut microbiota produces metabolites such as short-chain fatty acids (SCFAs), which can influence the development of obesity. Here Kimura et al.show that SCFAs act via the receptor GPR43, which acts as a sensor for excessive dietary energy and controls body energy utilization as well as metabolic homoeostasis.
- Ikuo Kimura
- , Kentaro Ozawa
- & Gozoh Tsujimoto
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α-SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPKα in vitro
The energy-sensing kinase AMPK is regulated by phosphorylation, however, the identity of AMPK phosphatases remains uncertain. Here the authors show that α-SNAP, a protein previously known for its role in membrane fusion, can dephosphorylate AMPK despite lacking a recognizable phosphatase domain.
- Lifu Wang
- & David L. Brautigan
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Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction
The emotional state of humans depends on the temporal concentration of neurochemicals. Blouin et al. measure temporal changes in two neuropeptides, hypocretin and melanin-concentrating hormone, and find that hypocretin but not melanin-concentrating hormone is linked to positive emotions and social interaction.
- Ashley M. Blouin
- , Itzhak Fried
- & Jerome M. Siegel
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De novo lipogenesis in human fat and liver is linked to ChREBP-β and metabolic health
Changes in the biosynthesis of fatty acids can influence tissue insulin sensitivity and the development of metabolic diseases. Eissing and colleagues show that de novolipogenesis in liver and adipose tissue is linked to metabolic health in humans and can be modulated by bariatric surgery.
- Leah Eissing
- , Thomas Scherer
- & Ludger Scheja
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A novel pathway for the production of hydrogen sulfide from D-cysteine in mammalian cells
Hydrogen sulphide is a signalling molecule with cytoprotective activity in mammals. Here, Kimura and colleagues identify a new biosynthetic pathway for the production of hydrogen sulphide from D-cysteine, which is shown to protect mouse kidneys from oxidative stress after ischaemia/reperfusion injury.
- Norihiro Shibuya
- , Shin Koike
- & Hideo Kimura
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Splicing factor SRSF3 is crucial for hepatocyte differentiation and metabolic function
Splicing factors, such as the protein SRSF3, regulate mRNA metabolism but are hard to study in vivobecause genetic kockouts are usually lethal. Here, Sen and colleagues create mice with a hepatocyte-specific knockout of Srsf3 and demonstrate its role in hepatocyte differentiation and liver function.
- Supriya Sen
- , Hassan Jumaa
- & Nicholas J. G. Webster
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Activity of the mitochondrial calcium uniporter varies greatly between tissues
The flow of calcium into the mitochondrial matrix is mediated by the mitochondrial calcium uniporter. Fieniet al. apply patch-clamp techniques to mitoplasts isolated from different mouse and Drosophilatissues and find that the mitochondrial calcium uniporter activity varies depending on the tissue studied.
- Francesca Fieni
- , Sung Bae Lee
- & Yuriy Kirichok
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Receptor tyrosine kinase ErbB2 translocates into mitochondria and regulates cellular metabolism
ErbB2 is a receptor tyrosine kinase that localizes to the plasma membrane. Dinget al. now show that ErbB2 also localizes to mitochondria, where it regulates mitochondrial respiratory function and resistance to cancer chemotherapy.
- Yan Ding
- , Zixing Liu
- & Ming Tan
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| Open Access
In silico method for modelling metabolism and gene product expression at genome scale
To describe the biochemical composition of an organism multiple data sets must be combined and this information can then be used forin silico analysis. By combining metabolism and transcription data, Lerman et al. discovered new regulons and improved the gene annotation for the simple organism Thermotoga maritima.
- Joshua A. Lerman
- , Daniel R. Hyduke
- & Bernhard O. Palsson
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Impaired thermogenesis and adipose tissue development in mice with fat-specific disruption of insulin and IGF-1 signalling
Insulin and insulin-like growth factor 1 signalling pathways have overlapping effects on adipose tissue and glucose homeostasis. Boucheret al.created fat-specific double knockouts of these pathways and demonstrated their crucial role for adipocyte development, metabolism and thermogenesis in mice.
- Jeremie Boucher
- , Marcelo A. Mori
- & C. Ronald Kahn
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| Open Access
The translation inhibitor pateamine A prevents cachexia-induced muscle wasting in mice
Cachexia, or muscle-wasting syndrome, is often observed in patients with cancer or sepsis, and no specific treatment of cachexia is currently available. In this study, Di Marcoet al.show that low doses of pateamine A, an inhibitor of translation initiation, prevent cachexia in a mouse model of the disease.
- Sergio Di Marco
- , Anne Cammas
- & Imed Eddine Gallouzi
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| Open Access
The Eutherian Armcx genes regulate mitochondrial trafficking in neurons and interact with Miro and Trak2
Mitochondrial dynamics and trafficking are important for providing energy for neuron function. In this study, the Armadillo repeat containing proteins clustered on the X chromosome are shown to be highly expressed in the nervous system and have a role in mitochondrial dynamics.
- Guillermo López-Doménech
- , Román Serrat
- & Eduardo Soriano
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miR-484 regulates mitochondrial network through targeting Fis1
Abnormal mitochondrial fission leads to apoptosis and disease. Li and colleagues reveal the mechanism with which the transcription factor Foxo3a suppresses Fis1-mediated mitochondrial fission and apoptosis in cardiomyocytes and adrenocortical cancer cells, which involves miR-484 inhibition of Fis1 translation.
- Kun Wang
- , Bo Long
- & Pei-Feng Li
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| Open Access
γ-Glutamylcysteine detoxifies reactive oxygen species by acting as glutathione peroxidase-1 cofactor
Glutathione's key role as a modulator of reactive oxygen species levels has recently been challenged. Quintana-Cabreraet al. now provide in vivoevidence supporting an antioxidant and neuroprotective function for γ-glutamylcysteine, which replaces glutathione by acting as glutathione peroxidase-1 cofactor.
- Ruben Quintana-Cabrera
- , Seila Fernandez-Fernandez
- & Juan P. Bolaños
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Phosphatidylinositol(4,5)bisphosphate coordinates actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane of chromaffin cells
The role of phosphatidylinositol(4,5)bisphosphate in exocytosis is unclear. This study shows that inhibition of the p110δ isoform of PI3-kinase promotes a transient increase in phosphatidylinositol(4,5)bisphosphate, leading to a potentiation of exocytosis in chromaffin cells.
- Peter J. Wen
- , Shona L. Osborne
- & Frédéric A. Meunier
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| Open Access
The rice mitochondrial iron transporter is essential for plant growth
Increasing the nutritional content of plant crops and the identification of iron transporters in rice would facilitate the improvement of rice varieties. In this study, the authors identify a mitochondrial iron transporter in rice — MIT — and suggest that this gene is important for rice growth and development.
- Khurram Bashir
- , Yasuhiro Ishimaru
- & Naoko K. Nishizawa
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| Open Access
The nuclear orphan receptor Nr4a2 induces Foxp3 and regulates differentiation of CD4+ T cells
Regulatory T cells are characterized by the expression of Foxp3, however, how the expression of this protein is controlled is unclear. Here, the authors show that the nuclear orphan receptor, Nr4a2, is a transcriptional activator of Foxp3, and suggest that it is required for the function of regulatory T cells.
- Takashi Sekiya
- , Ikkou Kashiwagi
- & Akihiko Yoshimura
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Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains
The integration of microarray and metabolite data is important for understanding the physiology of model organisms. This study demonstrates how the integration of these kinds of data can provide novel insights into the growth and protein metabolism of two different yeast strains.
- André B. Canelas
- , Nicola Harrison
- & Jens Nielsen
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| Open Access
TRPM7 is essential for Mg2+ homeostasis in mammals
Magnesium is an essential element of the diet and is a cofactor for many enzymes. In this study, the channel kinase TRPM7 is shown to be essential for magnesium homeostasis, and heterozygous mice lacking the kinase domain show a defect in absorption of magnesium from the diet.
- Lillia V. Ryazanova
- , Lusliany J. Rondon
- & Alexey G. Ryazanov
Acidosis overrides oxygen deprivation to maintain mitochondrial function and cell survival