Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

List by Pablo Ranea Robles


Integration of high-content fluorescence imaging into the metabolic flux assay reveals insights into mitochondrial properties and functions

Andrew C. Little, Ilya Kovalenko, Laura E. Goo, Hanna S. Hong, Samuel A. Kerk, Joel A. Yates, Vinee Purohit, David B. Lombard, Sofia D. Merajver, Costas A. Lyssiotis

Little et al. show here a method to integrate cellular metabolism studies with SeaHorse together with fluorescent dyes that allow to add information about mitochondrial dynamics and mitochondrial function.

ER stress sensor Ire1 deploys a divergent transcriptional program in response to lipid bilayer stress

Nurulain Ho, Haoxi Wu, Jiaming Xu, Jhee Hong Koh, Wei Sheng Yap, Wilson Wen Bin Goh, Shu Chen Chong, Stefan Taubert, Guillaume Thibault

The unfolded protein response (UPR) is an important mechanism to maintain homeostasis against misfolded proteins. However, alterations in lipid metabolism and composition have been linked to an activation of the UPR and ER stress. Here, Ho et al. uncovered a distinct UPR against lipid stress, caused by modifications in the lipid composition of ER membrane. This mechanism is conserved in yeasts and C. elegans, and involves the UPR transducer protein IRE1.

Modulation of muscle cell Insr and insulin receptor signaling by hyperinsulinemia in vitro and in vivo

Haoning Howard Cen, José Diego Botezelli, Su Wang, James D. Johnson

This preprint shed light on the mechanism of insulin resistance and its relation to hyperinsulinemia in muscle cells. They show that insulin receptor (Insr) levels were negatively correlated to insulin levels in muscle cells and mouse skeletal muscle, which suggest that hyperinsulinemia causes insulin resistance rather than being a compensatory mechanism.

Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+-dependent death of cancer cells

Francesco Ciscato, Riccardo Filadi, Ionica Masgras, Marco Pizzi, Oriano Marin, Nunzio Damiano, Paola Pizzo, Alessandro Gori, Federica Frezzato, Livio Trentin, Paolo Bernardi, Andrea Rasola

Ciscato et al. report that isoform 2 of the glycolytic enzyme hexokinase (HK2) is located in the mitochondrial-associated membranes (MAM), which are contact sites between the endoplasmic reticulum and mitochondria. They found that HK2 displacement from MAMs induce selective death of chronic lymphocytic leukemia B cells isolated from patients. Targeting the localization of HK2 in MAM reduced growth of breast and colon cancer cells in mice allografted with these cells.

mTORC1 signaling is not essential for the maintenance of muscle mass and function in adult sedentary mice

Alexander S Ham, Kathrin Chojnowska, Lionel A Tintignac, Shuo Lin, Alexander Schmidt, Daniel J Ham, Michael Sinnreich, Markus A Ruegg

Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of protein homeostasis in the muscle. Rapamycin, an mTOR inhibitor, is widely used but its effect on muscle mass are not well known yet. To elucidate the role of mTORC1 in maintaining muscle mass in adulthood, Ham et al. inhibited mTORC1 signaling in the skeletal muscle of adult mice. They inhibited mTORC1 by ablating Raptor, a regulator of mTORC1 signaling. They found that muscle mass and function were not affected at 5 months of age, suggesting that muscle maintenance in sedentary mice does not require mTORC1 activity.

Lecithin:Retinol Acyl Transferase (LRAT) induces the formation of lipid droplets

Martijn R. Molenaar, Tsjerk A. Wassenaar, Kamlesh K. Yadav, Alexandre Toulmay, Muriel C. Mari, Lucie Caillon, Aymeric Chorlay, Maya W. Haaker, Richard W. Wubbolts, Martin Houweling, A. Bas Vaandrager, Fulvio Reggiori, Abdou Rachid Thiam, William A. Prinz, J. Bernd Helms

Lipid droplets (LD) are cellular organelles that store neutral lipids usually composed of triacylglycerols and steryl esters, surrounded by a phospholipid layer. In this study, Molenaar et al. show that retinyl esters (which contain retinol, or vitamin A) are sufficient to drive the formation of lipid droplets in yeasts and mammalian cells.

The expanded BXD family of mice: A cohort for experimental systems genetics and precision medicine

David G. Ashbrook, Danny Arends, Pjotr Prins, Megan K. Mulligan, Suheeta Roy, Evan G. Williams, Cathleen M. Lutz, Alicia Valenzuela, Casey J. Bohl, Jesse F. Ingels, Melinda S. McCarty, Arthur G. Centeno, Reinmar Hager, Johan Auwerx, Saunak Sen, Lu Lu, Robert W. Williams

Studies in mice provide many advantages to investigate mechanisms and therapies for human diseases, but the mapping of genetic variation into phenotype is limited in inbred congenic strains. BXD mice population (originated with a cross between a B6 mouse and a DBA mouse, hence BXD) is a panel of isogenic but diverse inbred strains of mice. This allows to study very precisely genetic modulators of many traits. Here, the BXD population has been expanded, and a deep phenome of these new strains is described. This resource is a must to study precision medicine and very useful for systems genetics of metabolism.

ORP5 Regulates Transport of Lipids and Calcium to Mitochondria at Endoplasmic Reticulum-Mitochondria Membrane Contact Sites

Leila Rochin, Cécile Sauvanet, Eeva Jääskeläinen, Audrey Houcine, Annukka Kivelä, Xingjie Ma, Eyra Marien, Jonas Dehairs, Julie Neveu, Romain Le Bars, Johannes Swinnen, David Bernard, David Tareste, Vesa M. Olkkonen, Francesca Giordano

The interplay between mitochondria and the endoplasmic reticulum (ER) is essential for a proper lipid metabolism. These organelles exchange lipids at membrane contact sites, but the mechanisms and the proteins involved in this exchange are poorly understood, especially in mammals. Here, Rochin et al. show that two oxysterol binding protein (OSBP)-related proteins, ORP5 and ORP8, mediate non-vesicular transport of phosphatidylserine and, only ORP5, calcium from the ER to mitochondria in mammalian cells.

Ammonia inhibits energy metabolism in astrocytes in a rapid and GDH2-dependent manner

Leonie Drews, Marcel Zimmermann, Rebecca E. Poss, Dominik Brilhaus, Laura Bergmann, Constanze Wiek, Roland P. Piekorz, Andreas P.M. Weber, Tabea Mettler-Altmann, Andreas S. Reichert

Hyperammonemia causes hepatic encephalopathy. One of the cells more disturbed by the excess of ammonia are astrocytes. However, the molecular mechanism of ammonia-induced neurological impairment is not clear. Here, Drews et al. show that ammonia fixation generates glutamate, by the action of GDH2, and impairs mitochondrial OXPHOS in a cellular model of HE. Inhibition of GDH2 or the reductive amination of alpha-ketoglutarate ameliorated mitochondrial dysfunction.

Marine metabolomics: a method for the non-targeted measurement of metabolites in seawater by gas-chromatography mass spectrometry

Emilia M Sogin, Erik Puskas, Nicole Dubilier, Manuel Liebeke

Seamet, a new metabolomics method to measure metabolites in seawater using GC/MS is described in this preprint. This method overcomes the limitations of salt in marine metabolomics.

Housing temperature influences exercise training adaptations in mice

Steffen H. Raun, Carlos H. Henriquez-Olguin, Iuliia Karavaeva, Mona Ali, Lisbeth L.V. Moller, Witold Kot, Josue L. Castro Mejia, Dennis Sandris Nielsen, Zach Gerhart-Hines, Erik A. Richter, Lykke Sylow

Another report on different physiological response of rodents under different housting temperatures.  Raun et al. show here that exercise-induced metabolic adaptations were blunted when mice were housed in thermoneutral conditions (30 °C).

Exercise does not induce browning of WAT at thermoneutrality and induces an oxidative, myogenic signature in BAT

Peter Aldiss, Jo E Lewis, Irene Lupini, David J Boocock, Amanda K Miles, Francis J P Ebling, Helen Budge, Michael E Symonds

Rodents are usually housed below their thermoneutral zone, but studies done at thermoneutrality show that their physiology is completely different, because brown adipose tissue (BAT) is hyperactive below thermoneutrality. Aldiss et al. show here that exercise does not induce browing of white adipose tissue (WAT) and a different response in BAT in rats housed at thermoneutrality (28 °C).

Spastin tethers lipid droplets to peroxisomes and directs fatty acid trafficking through ESCRT-III

Chi-Lun Chang, Aubrey V. Weigel, Maria S. Ioannou, H. Amalia Pasolli, C. Shan Xu, David R. Peale, Gleb Shtengel, Melanie Freeman, Herald F. Hess, Craig Blackstone, Jennifer Lippincott-Schwartz

Peroxisomes interact with other organelles within the cell, but how they do it remain largely unknown. Here Chang et al. describe a tether between peroxisomes and lipid droplets that transfer fatty acids.

Presynaptic boutons that contain mitochondria are more stable

Robert M. Lees, James D. Johnson, Michael C. Ashby

Mitochondria are crucial for energy generation in the central nervous system and their dysfunction is related to multiple neurodegenerative diseases. Here, Lees et al. show that presynapses with more mitochondria are more stable, which open new avenues of research on the role of cellular metabolism and bioenergetics on synaptic structural plasticity.

Mitochondria form cholesterol tethered contact sites with the Nucleus to regulate retrograde response

Radha Desai, Daniel A East, Liana Hardy, James Crosby, Manuel Rigon, Danilo Faccenda, María Soledad Alvarez, Arti Singh, Marta Mainenti, Laura Kuhlman Hussey, Robert Bentham, Gyorgy Szabadkai, Valentina Zappulli, Gurtej Dhoot, Lisa E Romano, Xia Dong, Anne Hamechar-Brady, J Paul Chapple, Roland A. Fleck, Gema Vizcay-Barrena, Kenneth Smith, Michelangelo Campanella

Mitochondria and the nucleus communicate with each other but the molecular mechanisms and the players involved in this communication are not well known yet. Desai et al. report here for the first time Nucleus-Associated Mitochondria, which establish a new paradigm in organellar communication.

Mitochondrial biogenesis is transcriptionally repressed in lysosomal lipid storage diseases

King Faisal Yambire, Lorena Fernandez-Mosquera, Robert Steinfeld, Christiane Muehle, Elina Ikonen, Ira Milosevic, Nuno Raimundo

Mitochondria and lysosomes are key organelles in lipid metabolism. Here, Faisal et al. show that mitochondrial biogenesis program is repressed in lysosomal storage disorders (LSDs), giving a plausible explanation of the mitochondrial defects usually found in patients with LSDs.

Mitochondria supply ATP to the ER through a mechanism antagonized by cytosolic Ca2+

Jing Yong, Helmut Bischof, Marina Siirin, Anne Murphy, Roland Malli, Randal J. Kaufman

Proteins are folded and trafficked in the endoplasmic reticulum, but these processes require energyt in the form of ATP. Yong et al. describe a new intracellular communication between the ER and mitochondria, antagonized by Ca2+ signaling, that provides mitochondrial ATP to the ER.

Anabolic SIRT4 exerts retrograde control over TORC1 signalling by glutamine sparing in the mitochondria

Eisha Shaw, Manasi Talwadekar, Nitya Mohan, Aishwarya Acharya, Ullas Kolthur-Seetharam

Shaw et al. provide here a novel role of SIRT4 in the activation of mTORC1 in the fed state. Fine tuning of cellular metabolism is essential to maintain homeostasis in the transition between fed and fasted states. Here, they show that SIRT4 inhibits the conversion of glutamine to alpha-ketoglutarate in the mitochondria, which potentiates mTORC1 signaling, and regulates lipogenesis, autophagy and cell proliferation.

A comprehensive plasma metabolomics dataset for a cohort of mouse knockouts within the international mouse phenotyping consortium

Dinesh K Barupal, Ying Zhang, Tong Shen, Sili Fan, Bryan S Roberts, Patrick Fitzgerald, Benjamin Wancewicz, Luis Valdiviez, Gert Wohlgemuth, Gregory Byram, YingYng Choy, Bennett Haffner, Megan R. Showalter, Arpana Vaniya, Clayton S Bloszies, Jacob S Folz, Tobias Kind, Oliver Fiehn

Vast resource of untargeted and targeted metabolomics data from 30 knockout mice from the IMPC (International Mouse Phenotyping Consortium). Barupal et al. collected 220 plasma samples and detected 832 unique structurally identified metabolites from 124 chemical classes. All the raw data has been made available for further studies in this preprint.

Categories: biochemistry , cell biology , pathology , physiology

Tags: lipid , metabolism , mitochondria , peroxisome

Posted on: 21st May 2019 , updated on: 24th September 2019

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