Article
Agriculture, Multidisciplinary
Biying Wang, Xiaoya Zhao, Tong Fu, Xiaoyi Chen, Xiaoyu Guo, Xianzhen Li, Fan Yang
Summary: A positively evolved Suc2 promoter (SUC 2p) with stronger promoter activity than the wild-type Suc2 promoter (SUC 2wtp) was obtained in this study. The strength of SUC 2p was modulated by different glucose concentrations, with significantly enhanced promoter activity at low glucose concentrations.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Microbiology
Agnese Kokina, Kristel Tanilas, Zane Ozolina, Karlis Pleiko, Karlis Shvirksts, Ilze Vamza, Janis Liepins
Summary: Purine starvation affects cellular morphology, metabolism, and transcriptome in budding yeast, leading to cell cycle arrest, trehalose accumulation, and tolerance to environmental stresses. It also results in significant downregulation of ribosomal biosynthesis genes. The expression of new proteins during purine starvation is critical for cells to attain stress tolerance phenotype.
Article
Multidisciplinary Sciences
Weijing Yao, Yixing Li, Yingcong Chen, Yuting Chen, Pengwei Zhao, Yi Zhang, Qiang Jiang, Yuyao Feng, Fan Yang, Choufei Wu, Huiming Zhong, Yiting Zhou, Qiming Sun, Liqin Zhang, Wei Liu, Cong Yi
Summary: The DNA damage sensor Mec1 plays an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. It forms puncta and contacts both mitochondria and the phagophore assembly site (PAS) through interactions with the adaptor protein Ggc1 and direct binding with Atg13, respectively. These interactions are mediated by specific protein regions, MBR on Atg13 and ABR on Mec1, and disruption of these regions impairs the recruitment of Mec1 puncta and Atg13 to the PAS, blocking glucose starvation-induced autophagy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Yongook Lee, Bongkeun Kim, Hae-Soo Jang, Won-Ki Huh
Summary: Macroautophagy/autophagy is a crucial degradation pathway that cells use to maintain homeostasis and survive under stressful conditions. It has been discovered that Atg1-dependent phosphorylation of Vps34 is necessary for robust autophagy activity in yeast. This phosphorylation occurs at multiple serine/threonine residues in the helical domain of Vps34 in complex I and is essential for autophagy activation and cell survival. Furthermore, the localization of Vps34 complex I to the phagophore assembly site (PAS) is responsible for the complex I-specific phosphorylation of Vps34 and affects the dynamics of Atg18 and Atg8 at the PAS.
Article
Cell Biology
Bongkeun Kim, Yongook Lee, Hyojeong Choi, Won-Ki Huh
Summary: Tps2 functions as a positive regulator of autophagy in yeast cells by regulating the induction of ATG8, through controlling the activity of Ume6, Rim15, and Bmh1/2 proteins.
Article
Multidisciplinary Sciences
Juan Facundo Gulias, Florencia Niesi, Martin Aran, Susana Correa-Garcia, Mariana Bermudez-Moretti
Summary: Aging is a gradual decline in physiological integrity, which impairs functionality and increases mortality susceptibility. Dietary restriction, a known intervention to slow down aging, mimics nutrient scarcity without causing malnutrition. This study investigated the role of the transcription factor Gcn4 in the aging process of S. cerevisiae cells. The absence of Gcn4 led to various physiological changes, including increased mitochondrial activity and reactive oxygen species accumulation. Additionally, the mutant cells exhibited reduced ethanol production and lower levels of trehalose and free amino acids, disrupting cellular homeostasis and ultimately leading to a shortened lifespan.
Review
Microbiology
Muhammad Luqman Nasaruddin, Khaizurin Tajul Arifin
Summary: This scoping review identified a common pathway undertaken by S. cerevisiae under nutritional stress through the application of metabolomics. Changes in cellular nucleoside concentration were observed during nitrogen and glucose starvation, indicating the importance of autophagy in maintaining survival. The practicality of metabolomics in understanding underlying mechanisms for maintaining homeostasis and potential intervention targets against diseases was highlighted.
Article
Multidisciplinary Sciences
Kino Kusama, Yuta Suzuki, Ena Kurita, Tomoyuki Kawarasaki, Keisuke Obara, Fumihiko Okumura, Takumi Kamura, Kunio Nakatsukasa
Summary: Ribosome biogenesis (Ribi) is a complex and energy-consuming process that should be repressed under nutrient-limited conditions. This study reveals that degradation of Dot6 and Tod6 proteins ensures an appropriate level of Ribi gene expression and translation activity for cell survival under nutrient-limited conditions, through the regulation of Ribi gene expression and translation activity.
Article
Biochemistry & Molecular Biology
Zhiqiang Zhang, Ines Cottignie, Griet Van Zeebroeck, Johan M. Thevelein
Summary: Multiple starvation-induced, high-affinity nutrient transporters in yeast act as receptors for activation of the PKA pathway upon re-addition of their substrates. These transceptors physically interact with the PKA-related Sch9 protein kinase, suggesting a nutrient transceptor-Sch9-TOR axis that may be affected by environmental challenges.
BIOCHEMICAL JOURNAL
(2021)
Article
Biotechnology & Applied Microbiology
Francesca Gambacorta, Ellen R. Wagner, Tyler B. Jacobson, Mary Tremaine, Laura K. Muehlbauer, Mick A. McGee, Justin J. Baerwald, Russell L. Wrobel, John F. Wolters, Mike Place, Joshua J. Dietrich, Dan Xie, Jose Serate, Shabda Gajbhiye, Lisa Liu, Maikayeng Vang-Smith, Joshua J. Coon, Yaoping Zhang, Audrey P. Gasch, Daniel Amador-Noguez, Chris Todd Hittinger, Trey K. Sato, Brian F. Pfleger
Summary: Metabolic engineering strategies have been used to enhance isobutanol production in Saccharomyces cerevisiae, with pathway localization and redox cofactor balancing significantly affecting isobutanol titers. Mitochondrial localization and redox-imbalanced pathways were found to be more favorable for isobutanol production.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2022)
Article
Microbiology
Caoimhe E. O'Brien, Joao Oliveira-Pacheco, Eoin O Cinneide, Max A. B. Haase, Chris Todd Hittinger, Thomas R. Rogers, Oscar Zaragoza, Ursula Bond, Geraldine Butler
Summary: The study analyzed 77 isolates of Candida tropicalis and found a wide range of genetic diversity, with some isolates being highly heterozygous hybrids formed through mating between different parents. The hybrids were more commonly found in environmental niches rather than clinical settings, suggesting that hybridization is not linked to virulence in this species. Additionally, a genomic variant required for growth on specific amino acids was identified through genotype-phenotype correlation and CRISPR-Cas9 editing.
Review
Biology
Ritu Gupta, Sunil Laxman
Summary: The study reveals complex responses of cells to phosphate limitation, with extensive understanding of long-term effects but lacking a systems-level perspective. By categorizing phosphate utilization into cycles, sources, and sinks using yeast metabolic networks, metabolic reactions leading to sources or sinks of phosphate can be identified to illustrate how cells manage phosphate availability during transient limitations.
Article
Biochemistry & Molecular Biology
Ifeoluwapo Matthew Joshua, Meng Lin, Ariestia Mardjuki, Alessandra Mazzola, Thomas Hoefken
Summary: The p21-activated kinases (PAKs) are important signaling proteins that contribute to various cellular processes and human diseases. By studying the yeast PAK Ste20, researchers identified 56 proteins, mostly undocumented, that interact with Ste20. Ste20 plays a significant role in glucose metabolism and gene expression and induces filamentous growth through interaction with nuclear proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Gema Gonzalez-Rubio, Humberto Martin, Maria Molina
Summary: This study demonstrates that the absence of Ptc1 protein phosphatase leads to the upregulation of the MAPK pathway and causes various functional defects in Saccharomyces cerevisiae. Additionally, it shows that the absence of Ptc1 also results in impaired mitochondrial inheritance and perturbed cell cycle progression, along with other physiological alterations including mitochondrial hyperpolarization and ROS accumulation.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Natalie M. Garza, Aaron T. Griffin, Mohammad Zulkifli, Chenxi Qiu, Craig D. Kaplan, Vishal M. Gohil
Summary: This study identified novel genetic regulators of mitochondrial copper homeostasis through a genome-wide screen, including subunits of the AP-3 complex and components of the cellular pH-sensing pathway. These genes impact vacuolar acidity, which in turn perturbs mitochondrial copper homeostasis and CcO function. The study provides insights into how vacuolar pH affects mitochondrial respiration through copper homeostasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Anne Loft, Soren Fisker Schmidt, Giorgio Caratti, Ulrich Stifel, Jesper Havelund, Revathi Sekar, Yun Kwon, Alba Sulaj, Kan Kau Chow, Ana Jimena Alfaro, Thomas Schwarzmayr, Nikolaj Rittig, Mads Svart, Foivos-Filippos Tsokanos, Adriano Maida, Andreas Blutke, Annette Feuchtinger, Niels Moller, Matthias Blueher, Peter Nawroth, Julia Szendroedi, Nils J. Faergeman, Anja Zeigerer, Jan Tuckermann, Stephan Herzig
Summary: This study investigates the contribution of immune cells to metabolic homeostasis during fasting in healthy subjects. It identifies the glucocorticoid receptor (GR) as a key driver of fasting-induced reprogramming of the macrophage secretome, and shows that lack of macrophage GR impairs induction of ketogenesis during fasting and endotoxemia. This research also highlights the direct influence of liver macrophages on ketogenesis in hepatocytes, providing insights into the immune system's role in regulating metabolic activity during inflammatory diseases and infection.
Article
Gastroenterology & Hepatology
Mette K. Andersen, Line Skotte, Emil Jorsboe, Ryan Polito, Frederik F. Staeger, Peter Aldiss, Kristian Hanghoj, Ryan K. Waples, Cindy G. Santander, Niels Grarup, Inger K. Dahl-Petersen, Lars J. Diaz, Maria Overvad, Ninna K. Senftleber, Bolette Soborg, Christina V. L. Larsen, Clara Lemoine, Oluf Pedersen, Bjarke Feenstra, Peter Bjerregaard, Mads Melbye, Marit E. Jorgensen, Nils J. Faergeman, Anders Koch, Thomas Moritz, Matthew P. Gillum, Ida Moltke, Torben Hansen, Anders Albrechtsen
Summary: Adults with sucrase-isomaltase deficiency have better metabolic health, with lower BMI, body weight, fat percentage, fasting triglyceride, and remnant cholesterol levels. This is likely mediated by higher levels of acetate and reduced sucrose uptake, but not lower caloric intake.
Article
Biochemistry & Molecular Biology
Maria Gockert, Manfred Schmid, Lis Jakobsen, Marvin Jens, Jens S. Andersen, Torben Heick Jensen
Summary: This study investigates the consequences of acute losses of the adaptors NEXT and PAXT, as well as core exosome components, revealing a specific intron degradation phenotype in long-term NEXT depletion samples and an alternative mode of RNA decay independent of the core exosome.
NUCLEIC ACIDS RESEARCH
(2022)
Meeting Abstract
Endocrinology & Metabolism
Julia Bandres-Meriz, Christina Kunz, Jesper Havelund, Nils J. Faergeman, Irene Hurtado De Mendoza, Alejandro Majali-Martinez, Regina Ensenauer, Gernot Desoye
Article
Cell Biology
Dalia Ali, Florence Figeac, Atenisa Caci, Nicholas Ditzel, Clarissa Schmal, Greet Kerckhofs, Jesper Havelund, Nils Faergeman, Alexander Rauch, Michaela Tencerova, Moustapha Kassem
Summary: This study investigated the combined effects of obesity and estrogen deficiency on the skeleton. By feeding ovariectomized mice with a high-fat diet, it was found that obesity and estrogen deficiency can impair bone formation and decrease bone mass, leading to increased bone fragility.
Article
Endocrinology & Metabolism
Julia Bandres-Meriz, Christina Kunz, Jesper F. Havelund, Nils J. Faergeman, Alejandro Majali-Martinez, Regina Ensenauer, Gernot Desoye
Summary: The study found that the metabolome of pregnant women with overweight/obesity is already altered early in pregnancy due to changes in C-peptide. Lipid and amino acid metabolites related to obesity and insulin play a key role in these alterations.
INTERNATIONAL JOURNAL OF OBESITY
(2023)
Article
Biochemistry & Molecular Biology
Jerome O. Rouviere, Anna Salerno-Kochan, Soren Lykke-Andersen, William Garland, Yuhui Dou, Om Rathore, Ewa Smidova Molska, Guifen Wu, Manfred Schmid, Andrii Bugai, Lis Jakobsen, Kristina Zumer, Patrick Cramer, Jens S. Andersen, Elena Conti, Torben Heick Jensen
Summary: The RNA-binding ARS2 protein is involved in both early RNA polymerase II (RNAPII) transcription termination and transcript decay. It binds to ZC3H4 to recruit it to chromatin for RNAPII termination and forms a direct connection to the NEXT complex for rapid degradation of the RNA. ARS2 functions differently at CPA-instructed termination sites.
Article
Multidisciplinary Sciences
Astrid L. Basse, Karen N. Nielsen, Iuliia Karavaeva, Lars R. Ingerslev, Tao Ma, Jesper F. Havelund, Thomas S. Nielsen, Mikkel Frost, Julia Peics, Emilie Dalbram, Morten Dall, Juleen R. Zierath, Romain Barres, Nils J. Faergeman, Jonas T. Treebak, Zachary Gerhart-Hines
Summary: NAMPT controls the molecular clock and metabolic biorhythms in a tissue-specific manner. It plays a key role in the amplitude of the core clock in brown adipose tissue, has moderate dependence on NAD+ biosynthesis in white adipose tissue, and is completely refractory to loss in skeletal muscle. NAMPT also differentially orchestrates oscillation of clock-controlled gene networks and metabolite levels in different tissues.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Niels Boegholm, Narcis A. Petriman, Marta Loureiro-Lopez, Jiaolong Wang, Miren Itxaso Santiago Vela, Beibei Liu, Tomoharu Kanie, Roy Ng, Peter K. Jackson, Jens S. Andersen, Esben Lorentzen
Summary: Cilia are important cellular organelles for signaling and motility and are constructed via intraflagellar transport (IFT). RabL2 localizes to the basal body of cilia via an interaction with CEP19 before downstream association with the IFT machinery. Reconstituted pentameric IFT complex containing IFT81/74 enhances the GTP hydrolysis rate of RabL2. Structural models of RabL2-containing IFT complexes validate the architectural understanding of RabL2 incorporation into the IFT complex.
Article
Medicine, Research & Experimental
Vignesh Ramesh, Paradesi Naidu Gollavilli, Luisa Pinna, Mohammad Aarif Siddiqui, Adriana Martinez Turtos, Francesca Napoli, Yasmin Antonelli, Aldo Leal-Egana, Jesper Foged Havelund, Simon Toftholm Jakobsen, Elisa Le Boiteux, Marco Volante, Nils Joakim Faergeman, Ole N. Jensen, Rasmus Siersbaek, Kumar Somyajit, Paolo Ceppi
Summary: This study found an inverse association between short-chain fatty acids and EMT in non-small cell lung cancer patients. In vitro experiments showed that propionate treatment enhanced the epithelial transcriptional program and reduced the EMT phenotype in lung cancer cell lines. Animal experiments also confirmed that propionate can reduce lung cancer metastasis and lymph node spread. Further mechanistic investigation revealed that propionate treatment caused chromatin remodeling through p300-mediated histone acetylation.
EMBO MOLECULAR MEDICINE
(2023)
Article
Cell Biology
Patrik Polak, William Garland, Om Rathore, Manfred Schmid, Anna Salerno-Kochan, Lis Jakobsen, Maria Gockert, Piotr Gerlach, Toomas Silla, Jens S. Andersen, Elena Conti, Torben Heick Jensen
Summary: The RNA exosome is a versatile ribonuclease that functions in the nucleoplasm of mammalian cells. It is assisted by the nuclear exosome targeting (NEXT) complex and the poly(A) exosome targeting (PAXT) connection. The PAXT pathway targets short adenylated RNAs through the ZFC3H1 component, which interacts directly with ARS2. In addition, ZC3H18 competes with PAXT and antagonizes its activity.
Article
Cell Biology
Aida Rodriguez Lopez, Maria H. Jorgensen, Jesper F. Havelund, Frederic S. Arendrup, Srinivasa Prasad Kolapalli, Thorbjorn M. Nielsen, Eva Pais, Carsten Jorn Beese, Ahmad Abdul-Al, Anna Constance Vind, Jiri Bartek, Simon Bekker-Jensen, Marta Montes, Panagiotis Galanos, Nils Faergeman, Lotta Happonen, Lisa B. Frankel
Summary: Ribosomes are selectively targeted for degradation by autophagy during cell senescence, contributing to alterations in cell metabolome and the senescence-associated secretory phenotype.
Article
Endocrinology & Metabolism
Catarina Mendes Correia, Stine Marie Praestholm, Jesper Foged Havelund, Felix Boel Pedersen, Majken Storm Siersbaek, Morten Frendo Ebbesen, Zach Gerhart-Hines, Joerg Heeren, Jonathan Brewer, Steen Larsen, Blagoy Blagoev, Nils Joakim Faergeman, Lars Grontved
Summary: Hepatic lipid metabolism is affected by circadian regulation and disruption of the glucocorticoid receptor (GR) leads to hepatic steatosis. In this study, an acute hepatocyte-specific GR knockout model was used to investigate the role of GR in temporal hepatic lipid metabolism. Lipidomics analysis revealed impaired regulation of triglycerides, fatty acids, and sphingolipids in the absence of GR. Dysregulation of lipid metabolism was found to be associated with altered gene expression and increased lipid droplet formation.
Article
Genetics & Heredity
Emil Jorsboe, Mette K. Andersen, Line Skotte, Frederik F. Staeger, Nils J. Faergeman, Kristian Hanghoj, Cindy G. Santander, Ninna K. Senftleber, Lars J. Diaz, Maria Overvad, Ryan K. Waples, Frank Geller, Peter Bjerregaard, Mads Melbye, Christina V. L. Larsen, Bjarke Feenstra, Anders Koch, Marit E. Jorgensen, Niels Grarup, Ida Moltke, Anders Albrechtsen, Torben Hansen
Summary: The common Arctic-specific LDLR p.G137S variant is associated with increased risk of familial hypercholesterolemia (FH) and cardiovascular disease in Greenlanders, affecting up to 30% of the population.
HUMAN GENETICS AND GENOMICS ADVANCES
(2022)
Meeting Abstract
Endocrinology & Metabolism
P. M. Moller, M. H. Petersen, M. E. De Almeida, N. Ortenblad, J. Havelund, N. J. K. Faergeman, K. Hojlund