This virtual issue presents a collection of the most notable recent papers on metabolism selected by the editors of the four EMBO Press journals: EMBO Molecular Medicine, Molecular Systems Biology, EMBO Reports and The EMBO Journal.
The research findings touch on all aspects of metabolism: from the molecular mechanics of its regulation to adaptation at a systems level; from the physiological impact of the 'Atkins diet' to the regulation of the liver circadian clock by gut microbiobes. Discover the molecular control of food intake, the influence of diet and the gut microbiome on host physiology in health and disease, and metabolic adaptation of bacterial persisters. Catch up on the intricate links between mitochondrial function, muscle, ageing, and neurodegeneration, and on how a translation factor moonlights to control TORC1.
The collection provides a synthesis of the broad, inclusive scope of EMBO Press in publishing major advances in metabolism. All articles are free in October. We hope that you will enjoy reading it and welcome your own contributions.
|Modified Atkins diet induces subacute selective ragged-red-fiber lysis in mitochondrial myopathy patients
Sofia Ahola, Mari Auranen, Pirjo Isohanni, Satu Niemisalo, Niina Urho, Jana Buzkova, Vidya Velagapudi, Nina Lundbom, Antti Hakkarainen, Tiina Muurinen, Päivi Piirilä, Kirsi H Pietiläinen, Anu Suomalainen
High-fat low-carbohydrate modified Atkins diet (mAD) is a common weight-loss method, found to ameliorate mitochondrial myopathy in mice. In human patients, mAD induces muscle damage, especially of ragged-red fibers, the most affected by the disease.
EMBO Molecular Medicine (2016) DOI: 10.15252/emmm.201606592
|Bacterial persistence is an active σS stress response to metabolic flux limitation
Jakub Leszek Radzikowski, Silke Vedelaar, David Siegel, Álvaro Dario Ortega, Alexander Schmidt, Matthias Heinemann
Comprehensive and comparative phenotyping of bacterial persisters in two model systems shows that persistence is an active response with metabolic flux limitation at its core. The persister state is sustained through a system of feedback mechanisms.
Molecular Systems Biology (2016) DOI: 10.15252/msb.20166998
|Coupling of mitochondrial function and skeletal muscle fiber type by a miR-499/Fnip1/AMPK circuit
Jing Liu, Xijun Liang, Danxia Zhou, Ling Lai, Liwei Xiao, Lin Liu, Tingting Fu, Yan Kong, Qian Zhou, Rick B Vega, Min-Sheng Zhu, Daniel P Kelly, Xiang Gao, Zhenji Gan
Muscle contractile machinery and energy production system must be precisely coordinated to maintain function, but the underlying mechanisms are unclear. This study reveals that miR-499 in myosin gene couples mitochondrial function to muscle fiber type and ameliorates muscular dystrophy in mdx mice.
EMBO Molecular Medicine (2016) DOI: 10.15252/emmm.201606372
|Gut microbiota directs PPARγ‐driven reprogramming of the liver circadian clock by nutritional challenge
Mari Murakami, Paola Tognini, Yu Liu, Kristin L Eckel-Mahan, Pierre Baldi, Paolo Sassone-Corsi
High-fat diet-induced reprogramming in the mouse liver is driven by the gut microbiota through PPARγ. The microbiota in the gut exerts a distal effect on an otherwise non-cyclic liver metabolic and transcriptional program.
EMBO reports (2016) 17, 1292-1303
|ALS/FTD-associated FUS activates GSK‐3β to disrupt the VAPB-PTPIP51 interaction and ER-mitochondria associations
Radu Stoica, Sébastien Paillusson, Patricia Gomez-Suaga, Jacqueline C Mitchell, Dawn HW Lau, Emma H Gray, Rosa M Sancho, Gema Vizcay-Barrena, Kurt J De Vos, Christopher E Shaw, Diane P Hanger, Wendy Noble, Christopher CJ Miller
This study shows that FUS, by disrupting ER and mitochondria associations, regulates calcium uptake into and ATP production by mitochondria, with implications for amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD).
EMBO reports (2016) 17, 1326-1342
|Oligonucleotide-induced alternative splicing of serotonin 2C receptor reduces food intake
Zhaiyi Zhang, Manli Shen, Paul J Gresch, Masoud Ghamari‐Langroudi, Alexander G Rabchevsky, Ronald B Emeson, Stefan Stamm
The serotonin 2C receptor regulates food uptake and undergoes alternative pre-mRNA splicing; the ratio of the two spliced isoforms (truncated vs. full-length) controls the activity of serotonergic neurons. An oligonucleotide promotes the formation of the full-length receptor and reduces food intake.
EMBO Molecular Medicine (2016) 8, 878-894
|Mfn2 deficiency links age‐related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway
David Sebastián, Eleonora Sorianello, Jessica Segalés, Andrea Irazoki, Vanessa Ruiz-Bonilla, David Sala, Evarist Planet, Antoni Berenguer-Llergo, Juan Pablo Muñoz, Manuela Sánchez-Feutrie, Natàlia Plana, María Isabel Hernández-Álvarez, Antonio L Serrano, Manuel Palacín, Antonio Zorzano
Reduced muscle mitochondrial fusion protein Mfn2 is a determinant for age-induced decay of mitochondrial function and quality, contributing to age-associated metabolic alterations and sarcopenia.
The EMBO Journal (2016) 35, 1677-1693
|eIF4A inactivates TORC1 in response to amino acid starvation
Foivos-Filippos Tsokanos, Marie-Astrid Albert, Constantinos Demetriades, Kerstin Spirohn, Michael Boutros, Aurelio A Teleman
The eIF4A-containing eIF4F translation initiation complex negatively regulates TOR complex 1 activity in response to amino acid starvation, revealing a translation-independent function of eIF4F.
The EMBO Journal (2016) 35, 1058-1076
|Mitochondria are required for pro-ageing features of the senescent phenotype
Clara Correia-Melo, Francisco DM Marques, Rhys Anderson, Graeme Hewitt, Rachael Hewitt, John Cole, Bernadette M Carroll, Satomi Miwa, Jodie Birch, Alina Merz, Michael D Rushton, Michelle Charles, Diana Jurk, Stephen WG Tait, Rafal Czapiewski, Laura Greaves, Glyn Nelson, Mohammad Bohlooly-Y, Sergio Rodriguez-Cuenca, Antonio Vidal-Puig, Derek Mann, Gabriele Saretzki, Giovanni Quarato, Douglas R Green, Peter D Adams, Thomas von Zglinicki, Viktor I Korolchuk, João F Passos
Cellular senescence serves as an important anticancer growth arrest mechanism, but also contributes to ageing. This study shows that mitochondria are necessary for the pro-inflammatory phenotype during senescence and that senescence can be induced by mitochondrial biogenesis.
The EMBO Journal (2016) 35, 724-742
|The gut microbiota modulates host amino acid and glutathione metabolism in mice
Adil Mardinoglu, Saeed Shoaie, Mattias Bergentall, Pouyan Ghaffari, Cheng Zhang, Erik Larsson, Fredrik Bäckhed, Jens Nielsen
Tissue-specific genome-scale metabolic models (GEMs), transcriptomic and metabolomic analyses reveal global metabolic differences between conventionally raised and germ-free mice and show that the gut microbiota affects host amino acid and glutathione metabolism.
Molecular Systems Biology (2015) 11, 834