Review
Microbiology
Michael Lammers
Summary: Ac(et)ylation is a significant post-translational modification affecting essential cellular processes in all domains of life. It can occur at the ε-amino group of lysine side chains or at the α-amino group of proteins, and is involved in regulating protein function through various mechanisms including charge quenching, size alteration of lysine side chains, and interference with other modifications.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Soeren Kirchgaessner, Michael B. Braun, Natascha Bartlick, Cengiz Koc, Christopher D. Reinkemeier, Edward A. Lemke, Thilo Stehle, Dirk Schwarzer
Summary: Lysine acetylation is a post-translational modification of proteins, and a 1,2,4-triazole amino acid (ApmTri) has been identified as a mimic for acetyllysine (Kac) to recruit bromodomains (Brds) of the BET family. The optimization of ApmTri substituents and side chain spacing enabled BET Brds to bind to ApmTri-containing peptides with affinities similar to native substrates. The use of genetically encoded ApmTri allowed the study of BET proteins in vitro and in vivo by providing a stable Kac mimic that reflects charge neutralization and Brd recruitment.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Daniel Schator, Sonia Mondino, Jeremy Berthelet, Cristina Di Silvestre, Mathilde Ben Assaya, Christophe Rusniok, Fernando Rodrigues-Lima, Annemarie Wehenkel, Carmen Buchrieser, Monica Rolando
Summary: Legionella pneumophilia secretes more than 300 effectors, including RomA and LphD, via a type IV secretion system. RomA methylates histone H3 at K14 to counteract host immune responses, while LphD deacetylates H3K14 to work synergistically with RomA. The two effectors target host chromatin and bind the HBO1 histone acetyltransferase complex to regulate histone modifications.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Jessica Araujo, Sara Ottinger, Sumana Venkat, Qinglei Gan, Chenguang Fan
Summary: By studying acetylation, we have used the genetic code expansion approach to produce aconitase variants with specific acetylation sites, and found that acetylation has different effects on the enzyme activity of the two aconitase isozymes. We also found that both isozymes can be chemically acetylated by acetyl-phosphate and deacetylated by the CobB deacetylase.
FRONTIERS IN CHEMISTRY
(2022)
Review
Biochemistry & Molecular Biology
Nour Fatema, Chenguang Fan
Summary: Lysine acetylation is a common post-translational modification that plays a significant role in biological pathways. Proteomic analyses have identified numerous acetylation sites, but the specific functions of individual acetylation events remain unclear. To address this issue, the genetic code expansion technique has been utilized to generate site-specifically acetylated proteins, enabling the characterization of acetylation effects with minimal interferences. In this review, we summarize the development of this technique for lysine acetylation and discuss recent studies on lysine acetylation of citrate acid cycle enzymes in bacteria, highlighting its practical application in protein acetylation studies.
MOLECULAR MICROBIOLOGY
(2023)
Article
Microbiology
Victoria L. Barlow, Yu-Hsuan Tsai
Summary: This study investigates the effect of lysine acetylation on the DNA-binding protein HU in bacteria. The researchers found that acetylation at Lys86 can regulate the DNA binding ability of the HU homodimer. Specifically, Lys86 acetylation reduced the interaction with short double-stranded DNA containing a gap or nick, while enhancing the interaction with longer DNA fragments. These findings demonstrate the complexity of post-translational modifications and the role of lysine acetylation in bacterial gene transcription and epigenetic regulation.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ruotong Xiao, Lei Zhao, Hongpeng Ma, Qiaoli Liu, Hongqiang Qin, Xiaozhou Luo, Weimin Xuan
Summary: This study focuses on the importance of lysine acetylation in protein function and its association with diseases. By introducing an orthogonal lysine acylation and deacylation system, the researchers aim to precisely study the biological consequences of individual acetylation or deacetylation events in living cells, potentially opening up new avenues for in-depth biological applications.
Article
Biochemistry & Molecular Biology
Mehtap Cevik, Selen Caker, Gokce Deliorman, Penbe Cagatay, Meliha Koldemir Gunduz, Belgin Susleyici
Summary: This study found that glipizide can cause DNA damage in both mature and senescent adipocytes, and it has different effects on the expression of the Ran gene. Further research is needed to reveal the effect of glipizide on DNA and nuclear interactions at the molecular level.
MOLECULAR BIOLOGY REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Peter Borkuti, Ildiko Kristo, Aniko Szabo, Csaba Bajusz, Zoltan Kovacs, Zsuzsanna Rethi-Nagy, Zoltan Lipinszki, Tamas Lukacsovich, Sven Bogdan, Peter Vilmos
Summary: Actin, a fundamental protein, plays various roles in the nucleus and cytoplasm of eukaryotic cells. Our study in Drosophila revealed the essentiality of nuclear actin and the robustness of its nuclear localization, supported by a strong system. We also identified novel nuclear import factors specific to actin, shedding light on the mechanism behind its nuclear functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Cell Biology
Joanna Kalita, Larisa E. Kapinos, Roderick Y. H. Lim
Summary: This review examines the role of the nuclear pore complex in nucleocytoplasmic transport and discusses unresolved issues such as the partitioning of importin and exportin in the cytoplasm and nucleus, and the maintenance of the RanGTP-RanGDP gradient across the nuclear envelope.
JOURNAL OF CELL SCIENCE
(2021)
Article
Plant Sciences
Marina Naoumkina, Gregory N. Thyssen, David D. Fang, Christopher B. Florane, Ping Li
Summary: In this study, it was found that the elongation of fiber cells in the Ligon lintless-2 (Li-2) cotton mutant is inhibited by siRNAs. This inhibition is caused by a large structural rearrangement at the end of chromosome D13, which leads to the production of self-complementary transcripts and generation of siRNAs. This finding reveals the regulatory mechanism of the Ran Binding Protein 1 family in cotton fiber growth.
Article
Biotechnology & Applied Microbiology
Eden Ozer, Lital Alfonta
Summary: Escherichia coli has been the most commonly used model bacterium in research for decades, but a faster synthetic biology chassis, Vibrio natriegens, is now emerging. Established methodologies in E. coli are being adapted for V. natriegens to create a faster platform for molecular biology studies. Genetic code expansion, such as incorporating unnatural amino acids into proteins, is a powerful tool for protein engineering and biorthogonal modifications, and has been successfully adapted for V. natriegens.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Review
Materials Science, Biomaterials
Petra Neumann-Staubitz, Michael Lammers, Heinz Neumann
Summary: Lysine acylation is a widespread protein modification that influences protein function, but the majority of acylation sites are not yet characterized. Semi-synthetic methods and genetic code expansion techniques can aid in studying these modifications and discovering their potential applications in various fields.
Article
Chemistry, Multidisciplinary
David E. Wright, Nikolaus Panaseiko, Patrick O'Donoghue
Summary: After acetylation, TrxR1 shows increased resistance to oxidative inactivation and peroxide-induced multimer formation, and both site-specific and general acetylation can regulate the enzyme's ability to resist oxidative damage.
FRONTIERS IN CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Pearl Morosky, Cody Comyns, Lance G. A. Nunes, Christina Z. Z. Chung, Peter R. R. Hoffmann, Dieter Soll, Oscar Vargas-Rodriguez, Natalie Krahn
Summary: Post-translational modifications (PTMs) are crucial for regulating protein function in eukaryotes. Genetic code expansion (GCE) in bacteria is a strategy to study these modifications, as bacteria have low frequency of natural PTMs. By combining GCE with selenocysteine insertion technologies, a genetic system was created to study post-translational modifications in selenoproteins. This method allows for site-specific modification of multiple proteins and has the potential to advance our understanding of selenoprotein functions.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Hematology
Johanna Stachelscheid, Qu Jiang, Christoph Aszyk, Kathrin Warner, Nadine Bley, Tony Mueller, Olga Vydzhak, Konstantinos Symeonidis, Giuliano Crispatzu, Petra Mayer, Stuart James Blakemore, Gudrun Goehring, Sebastian Newrzela, Stephanie Hippler, Sandra Robrecht, Karl-Anton Kreuzer, Christian Pallasch, Marcus Krueger, Axel Lechner, Kirsten Fischer, Stephan Stilgenbauer, Dirk Beutner, Michael Hallek, Daniel Auguin, Stefan Huettelmaier, Johannes Bloehdom, Elena Vasyutina, Marco Herling
Summary: Upregulation of TCL1A is associated with various B-cell and T-cell malignancies. It exerts a strong transforming impact via nuclear topography. TCL1A interacts with cell cycle and DNA repair regulators, particularly CDC20, leading to accelerated cell cycle transition, chromosome missegregation, and cellular aneuploidy.
Article
Infectious Diseases
Faheem Ahmad Akif, Mona Mahmoud, Binod Prasad, Peter Richter, Azizullah Azizullah, Muhammad Qasim, Muhammad Anees, Marcus Krueger, Susanne Gastiger, Andreas Burkovski, Sebastian M. Strauch, Michael Lebert
Summary: Polyethylenimines (PEIs), a group of polycationic molecules, have antimicrobial activity and can enhance the antimicrobial activity of chlorophyllin against bacteria, especially under light conditions.
Article
Cell Biology
Soni Deshwal, Mashun Onishi, Takashi Tatsuta, Tim Bartsch, Eileen Cors, Katharina Ried, Kathrin Lemke, Hendrik Nolte, Patrick Giavalisco, Thomas Langer
Summary: The cytosolic lipid transfer protein STARD7 is identified as a critical factor for intracellular coenzyme Q transport and suppresses ferroptosis. Dual localization of STARD7 to mitochondria and cytosol ensures the synthesis of coenzyme Q and its transport to the plasma membrane. PARL-mediated STARD7 processing is necessary for coordinating coenzyme Q synthesis and cellular distribution and could be targeted to interfere with ferroptosis.
NATURE CELL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Anna Juliane Vesting, Alexander Jais, Paul Klemm, Lukas Steuernagel, Peter Wienand, Morten Fog-Tonnesen, Henning Hvid, Anna-Lena Schumacher, Christian Kukat, Hendrik Nolte, Theodoros Georgomanolis, Janine Altmueller, Manolis Pasparakis', Andreas Schmidt', Marcus Krueger', Marc Schmidt Supprian, Ari Waisman, Beate Katharina Straub, Nathanael Raschzok, Michel Bernier, Andreas L. Birkenfeld, Nadine Hoevelmeyer, Jens C. Bruening, F. Thomas Wunderlich
Summary: The non-canonical NFKB-inducing kinase (NIK/MAP3K14) plays a crucial role in metabolic nonalcoholic fatty liver disease (NAFLD) and the progression from NAFLD to hepatocellular carcinoma (HCC) by modulating JAK2/STAT5 signaling.
MOLECULAR METABOLISM
(2022)
Article
Clinical Neurology
Carolina Montoro-Gamez, Hendrik Nolte, Thibaut Molinie, Giovanna Evangelista, Simon E. Troeder, Esther Barth, Milica Popovic, Aleksandra Trifunovic, Branko Zevnik, Thomas Langer, Elena Rugarli
Summary: Montoro-Gamez et al. have developed a new mouse model for hereditary spastic paraplegia caused by mutations in the SPG7 gene. The model reproduces the phenotypic features of the disease and demonstrates a cerebellar-specific role for SARM1 in triggering axonal degeneration and neuroinflammation. The study reveals that the lack of SPG7 rewires the mitochondrial proteome, leading to decreased mito-ribosomal subunits and remodelling of mitochondrial solute carriers and transporters. Deletion of SARM1 delays the onset of symptoms, rescues mitochondrial swelling and axonal degeneration, and dampens neuroinflammation in a neuron-specific manner.
Article
Cell Biology
Weiyi Chen, Oliver Mehlkop, Alexandra Scharn, Hendrik Nolte, Paul Klemm, Sinika Henschke, Lukas Steuernagel, Tamara Sotelo-Hitschfeld, Ecem Kaya, Claudia Maria Wunderlich, Thomas Langer, Natalia L. Kononenko, Patrick Giavalisco, Jens Claus Bruening
Summary: This study found that fasting activates autophagy in the liver and AgRP neurons in the hypothalamus of mice. Activation of AgRP neurons induce autophagy, alter phosphorylation of autophagy regulators, and promote ketogenesis. The induction of liver autophagy by AgRP neurons relies on NPY release in the PVH via inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. This study reveals a fundamental regulatory principle of liver autophagy in controlling metabolic adaptation during nutrient deprivation.
Editorial Material
Biochemistry & Molecular Biology
Marcus Krueger
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Martin R. Spaeth, K. Johanna R. Hoyer-Allo, Lisa Seufert, Martin Hoehne, Christina Lucas, Theresa Bock, Lea Isermann, Susanne Brodesser, Jan-Wilm Lackmann, Katharina Kiefer, Felix C. Koehler, Katrin Bohl, Michael Ignarski, Petra Schiller, Marc Johnsen, Torsten Kubacki, Franziska Grundmann, Thomas Benzing, Aleksandra Trifunovic, Marcus Krueger, Bernhard Schermer, Volker Burst, Roman-Ulrich Mueller
Summary: By studying the kidneys of mice under conditions of hypoxia and caloric restriction (CR), researchers discovered the significant role of the KYNU gene in the nephroprotective effect of CR. They also found that CR induces a novel pathway for NAD+ synthesis, which was also observed in humans.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2023)
Article
Cell Biology
Pablo Rivera-Mejias, Alvaro Jesus Narbona-Perez, Lidwina Hasberg, Lara Kroczek, Amir Bahat, Steffen Lawo, Kat Folz-Donahue, Anna-Lena Schumacher, Sofia Ahola, Fiona Carola Mayer, Patrick Giavalisco, Hendrik Nolte, Sergio Lavandero, Thomas Langer
Summary: The flexibility of mitochondria metabolism is crucial for cell development, differentiation, and survival. The enzyme OMA1 is involved in regulating mitochondrial morphology and stress signaling, impacting tumorigenesis and cell survival in a cell- and tissue-specific manner. This study reveals that OMA1-dependent cell survival relies on metabolic cues. By conducting a metabolism-focused CRISPR screen and analyzing human gene expression data, it was found that OMA1 protects against DNA damage. The deficiency of nucleotides induced by chemotherapeutic agents leads to p53-dependent apoptosis in cells lacking OMA1. The protective effect of OMA1 is not dependent on its activation or its role in the processing of OPA1 and DELE1. OMA1-deficient cells exhibit reduced glycolysis and accumulate oxidative phosphorylation (OXPHOS) proteins following DNA damage. Inhibition of OXPHOS restores glycolysis and provides resistance against DNA damage. Thus, OMA1 plays a role in balancing cell death and survival through the control of glucose metabolism, shedding light on its involvement in cancerogenesis.
Editorial Material
Oncology
Marcus Krueger, Sascha Kopp
Review
Cell Biology
Thomas J. Corydon, Herbert Schulz, Peter Richter, Sebastian M. Strauch, Maik Boehmer, Dario A. Ricciardi, Markus Wehland, Marcus Krueger, Gilmar S. Erzinger, Michael Lebert, Manfred Infanger, Petra M. Wise, Daniela Grimm
Summary: Microgravity has a significant impact on the health of space explorers, affecting cell proliferation, differentiation, and growth. With the planning of deep space exploration and the commercialization of space travel, researchers are focusing on gene regulation in cells and organisms exposed to real and simulated microgravity. Cancer and metastasis research in particular benefit from these findings.
Review
Biochemistry & Molecular Biology
Silvana Miranda, Shannon Marchal, Lina Cumps, Jenne Dierckx, Marcus Kruger, Daniela Grimm, Sarah Baatout, Kevin Tabury, Bjorn Baselet
Summary: The lunar dust problem arose from NASA's Apollo missions in 1969, as exposure to lunar dust became unavoidable. Several astronauts suffered allergy-like symptoms due to lunar dust inhalation. Research into the toxic effects of lunar dust gained significant interest and expanded to include other organ systems. With plans for future moon missions and potentially Mars missions, dust mitigation strategies are crucial for sustainable space exploration.
Article
Multidisciplinary Sciences
Mengjie Zhu, Fabian Metzen, Mark Hopkinson, Janina Betz, Juliane Heilig, Jassi Sodhi, Thomas Imhof, Anja Niehoff, David E. Birk, Yayoi Izu, Marcus Krueger, Andrew A. Pitsillides, Janine Altmueller, Gerjo J. V. M. van Osch, Volker Straub, Gudrun Schreiber, Mats Paulsson, Manuel Koch, Bent Brachvogel
Summary: This study investigated the role of collagen XII in joint pathophysiology by analyzing collagen XII deficient mice and human patients. Collagen XII was found to be widely expressed in developing joints. Lack of collagen XII in mice destabilized tendons and femoral trochlear groove, leading to patellar subluxation. This clinical feature was also identified in human patients with collagen XII deficiency, providing an explanation for joint hyperlaxity.
Meeting Abstract
Dermatology
T. Leibing, C. Manta, J. Krzistetzko, M. Adrian, C. Kirkamm, C. Sticht, S. Tonack, H. Nolte, M. Krueger, S. Offermanns, K. Schledzewski, S. Goerdt, C. Geraud
EXPERIMENTAL DERMATOLOGY
(2023)
Article
Cell Biology
Jose Luis Cortes-Sanchez, Daniela Melnik, Viviann Sandt, Stefan Kahlert, Shannon Marchal, Ian R. D. Johnson, Marco Calvaruso, Christian Liemersdorf, Simon L. Wuest, Daniela Grimm, Marcus Krueger
Summary: In the preparation of space and microgravity experiments, the use of ground-based facilities for initial experiments and feasibility studies is common. One approach to simulate microgravity conditions on Earth is to use a random positioning machine (RPM) as a rotary bioreactor. Combined with a suitable low-mass model system, such as cell cultures, these devices have been shown to produce results similar to those obtained in actual space experiments under real microgravity conditions. The RPM serves as a simulator of microgravity by randomizing the impact of Earth's gravity vector especially for suspended cells, and it also simulates physiological shear forces on the adherent cell layer.
