Review
Cell Biology
Ewa Sikora, Anna Bielak-Zmijewska, Grazyna Mosieniak
Summary: Cellular senescence is a significant biological phenomenon that mainly participates in aging and aging-related diseases through secretion activity and cell cycle arrest. In this process, DNA damage, nuclear changes, and chromatin rearrangement play important roles.
AGEING RESEARCH REVIEWS
(2021)
Review
Biotechnology & Applied Microbiology
Azucena Rocha, Audrey Dalgarno, Nicola Neretti
Summary: The article provides an overview of the nuclear changes that occur in different forms of senescence, including changes in chromatin state and composition, three-dimensional organization of the genome, nuclear envelope, and accessibility of repetitive genomic regions. These changes are shared across all forms of senescence, indicating that nuclear organization plays a fundamental role in the senescent state and interaction of senescent cells with the surrounding tissue.
BRIEFINGS IN FUNCTIONAL GENOMICS
(2022)
Article
Biochemistry & Molecular Biology
Donghui Zhang, Yanmei Zhu, Yanmin Ju, Hongyong Zhang, Xiaopeng Zou, Shangrong She, Danping Zhu, Yiting Guan
Summary: Dramatic changes in chromatin structure occur during cellular senescence, affecting genome accessibility and transcription. This study investigates the redistribution of accessible chromatin regions during senescence and identifies the transcription factor TEAD4 as a key regulator of chromatin state and SASP gene transcription.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2023)
Review
Biology
Malgorzata Kloc, Priyanka Chanana, Nicole Vaughn, Ahmed Uosef, Jacek Z. Kubiak, Rafik M. Ghobrial
Summary: Actin plays crucial roles in the nucleus, including maintenance of nuclear structure, chromatin remodeling, DNA repair, and transcriptional regulation. Its multifaceted functions are essential for individual cell function, cell fate determination, tissue differentiation, and disease establishment.
Review
Cell Biology
Rashmi Upadhyay Pathak, Mamilla Soujanya, Rakesh Kumar Mishra
Summary: The metazoan nucleus is a highly structured organelle that can undergo abnormalities in morphology and architecture in aged cells. Computational image analysis of nuclear features offers a promising tool to evaluate physiological age of a cell and can be used to examine progression of age-related diseases and therapies.
AGEING RESEARCH REVIEWS
(2021)
Article
Microbiology
Quincy Rosemarie, Elijah Kirschstein, Bill Sugden
Summary: We have discovered how Epstein-Barr virus (EBV) induces the reorganization of cellular chromatin, with viral DNA replication occurring in the chromatin-free regions. Five families of DNA viruses induce similar reorganization, and they infect a variety of hosts. The viral genes and processes required for EBV's chromatin reorganization have been identified, and a two-step model for the process has been proposed. The importance of chromatin reorganization in viral life cycles is emphasized. Overall, a 9 out of 10 score is given for the importance of this research.
Review
Neurosciences
Yuki Fujita, Sarshan R. Pather, Guo-li Ming, Hongjun Song
Summary: This review explores the different aspects of spatial genome organization in the nervous system and its role in regulating gene expression, as well as its dysregulation in brain disorders. It also highlights new technologies used to study and manipulate chromatin architecture, and discusses the potential of investigating spatial genome organization for a better understanding of the nervous system and associated disorders.
Article
Cell Biology
Isabel N. Goronzy, Sofia A. Quinodoz, Joanna W. Jachowicz, Noah Ollikainen, Prashant Bhat, Mitchell Guttman
Summary: Mammalian genomes are organized into A/B compartments, and transcription occurs within B compartments with multiple active genes colocalizing. Genes proximal to nucleoli can also undergo transcription. This study provides important insights into the relationship between genome structure and transcription.
Article
Multidisciplinary Sciences
Abigail E. Loneker, Farid Alisafaei, Aayush Kant, David Li, Paul A. Janmey, Vivek B. Shenoy, Rebecca G. Wells
Summary: Matrix stiffening and external mechanical stress have been found to be linked to disease and cancer development. In this study, researchers treated human hepatocytes with oleate and found that lipid droplets are intracellular mechanical stressors, causing nuclear deformation, chromatin condensation, and impaired hepatocyte function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Ezequiel Nazer
Summary: Lamins are components of the nuclear lamina and play a role in transcriptional regulation and chromatin organization. Recent studies have shown that lamins not only regulate gene transcription in regions associated with the nuclear lamina, but also interact with promoters and enhancers located inside the nucleus. Functional studies suggest that lamins play a role in transcription and chromatin interactions of key developmental gene programs. This review focuses on the emerging non-canonical functions of lamins in Drosophila and mammals as model organisms.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2022)
Article
Engineering, Biomedical
Stephanie E. Schneider, Adrienne K. Scott, Benjamin Seelbinder, Courtney Van Den Elzen, Robert L. Wilson, Emily Y. Miller, Quinn I. Beato, Soham Ghosh, Jeanne E. Barthold, Jason Bilyeu, Nancy C. Emery, David M. Pierce, Corey P. Neu
Summary: Cells are continuously influenced by dynamic environmental cues, especially mechanical cues, which affect their behavior and can lead to morphological and behavioral changes in the nucleus. The nucleus shows a responsive behavior to mechanical forces, propagating from the substrate, and disruption of this behavior can have lasting consequences on cellular functioning. Using an in vitro model of traumatic neural injury, the study demonstrates the dynamic nuclear behavioral response to impulse stretch and highlights the changes in cellular and nuclear behavior caused by mechanical forces.
ACTA BIOMATERIALIA
(2023)
Article
Cell Biology
Michael H. Nichols, Victor G. Corces
Summary: Chromatin is organized in the nucleus via CTCF loops and compartmental domains, with distinct paradigms of compartmental domain formation identified in different cell types in human tissues. The forces driving compartmental domain formation in human cells are conserved, with diverse compartmentalization patterns attributed to differences in chromatin features. This study offers mechanistic insights into the fundamental forces driving the 3D organization of the genome, extending findings to suggest similar principles at work beyond humans.
Review
Hematology
Yang Mei, Yijie Liu, Peng Ji
Summary: A characteristic feature of terminal erythropoiesis in mammals is the expulsion of the highly condensed nucleus during red blood cell maturation. Recent studies have highlighted epigenetic modifications and histone release during chromatin condensation. Novel insights have been gained in enucleation, organelle clearance, and proteolysis mechanisms during reticulocyte maturation.
Article
Computer Science, Interdisciplinary Applications
Qing Cheng, Pourya Delafrouz, Jie Liang, Chun Liu, Jie Shen
Summary: In this study, a special phase field/diffusive interface method was developed to model the nuclear architecture reorganization process, with a Lagrange multiplier approach used to preserve specific physical and geometrical constraints for biological events. Several efficient and robust linear and weakly nonlinear schemes were developed for this new model, with ample numerical simulations presented to validate the model and numerical methods, reproducing processes of nuclear architecture reorganization from experimental literature.
JOURNAL OF COMPUTATIONAL PHYSICS
(2022)
Article
Multidisciplinary Sciences
Jun-Yeong Lee, Ian Davis, Elliot H. H. Youth, Jonghwan Kim, Gary Churchill, James Godwin, Ron Korstanje, Samuel Beck
Summary: Cellular aging is characterized by disruption of the nuclear lamina and its associated heterochromatin, with the activation of CGI(-) genes being a common feature of normal and pathological aging in mice and humans. This up-regulation of CGI(-) genes is directly responsible for age-related physiological deterioration, including increased secretion of inflammatory mediators.
Review
Biochemistry & Molecular Biology
Raphae Rodriguez, Stuart L. Schreiber, Marcus Conrad
Summary: Ferroptosis is a unique type of non-apoptotic cell death that occurs due to the unrestrained peroxidation of phospholipids, resulting in the production of lethal oxygen radicals mediated by iron. It has been observed in various organisms, including mammals, where it can serve as a defense mechanism against pathogens and be utilized by T cells for effective killing of tumor cells. Conversely, ferroptosis is considered to be one of the main cell death mechanisms contributing to degenerative diseases. Recent studies suggest that certain cancers exhibit vulnerabilities to ferroptosis, particularly in dedifferentiating and persister cancer cells that are dependent on iron. Exploiting this dependence on iron may hold therapeutic benefits.
Article
Immunology
Abdel A. Alli, Dhruv Desai, Ahmed Elshika, Marcus Conrad, Bettina Proneth, William Clapp, Carl Atkinson, Mark Segal, Louis A. Searcy, Nancy D. Denslow, Subhashini Bolisetty, Borna Mehrad, Laurence Morel, Yogesh Scindia
Summary: Ferroptosis, an iron-dependent form of cell death characterized by lipid peroxidation, has not received much attention in lupus nephritis. Our study found increased lipid peroxidation and elevated expression of pro-ferroptosis enzyme in the kidneys of lupus nephritis patients and mice. We also identified impaired iron sequestration and reduced expression of ferroptosis inhibitors in nephritic mice. Furthermore, we demonstrated that lupus nephritis patient serum can induce ferroptosis in human proximal tubular cells, which was inhibited by Liproxstatin-2. These findings highlight the importance of intra-renal ferroptosis in the pathogenesis of lupus nephritis.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
Bo Sun, Pawel Smialowski, Wasim Aftab, Andreas Schmidt, Ignasi Forne, Tobias Straub, Axel Imhof
Summary: Data-independent acquisition (DIA) of tandem mass spectrometry spectra is a promising technology to improve protein coverage and quantification in complex mixtures. The quality of spectral libraries used for database searching is crucial for the success of DIA experiments. A new algorithm called deep-learning for SWATH analysis (dpSWATH) has been developed to generate theoretical libraries for SWATH experiments, allowing for increased protein identification rate compared to traditional or library-free methods. dpSWATH is superior to other algorithms based on Orbitrap data in predicting SWATH-MS measurements.
Article
Multidisciplinary Sciences
Pedro Weickert, Hao-Yi Li, Maximilian J. Goetz, Sophie Duerauer, Denitsa Yaneva, Shubo Zhao, Jacqueline Cordes, Aleida C. Acampora, Ignasi Forne, Axel Imhof, Julian Stingele
Summary: DNA-protein crosslinks (DPCs) are common DNA lesions induced by reactive metabolites and chemotherapeutic agents. A novel technique called PxP is developed to identify and track different types of DPCs in mammalian cells. The study reveals an unexpected role for the SPRTN protease in replication-independent repair of DPCs and demonstrates the mechanisms involved.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Ilio Vitale, Federico Pietrocola, Emma Guilbaud, Stuart A. Aaronson, John M. Abrams, Dieter Adam, Massimiliano Agostini, Patrizia Agostinis, Emad S. Alnemri, Lucia Altucci, Ivano Amelio, David W. Andrews, Rami Aqeilan, Eli Arama, Eric H. Baehrecke, Siddharth Balachandran, Daniele Bano, Nickolai A. Barlev, Jiri Bartek, Nicolas G. Bazan, Christoph Becker, Francesca Bernassola, Mathieu J. M. Bertrand, Marco E. Bianchi, Mikhail V. Blagosklonny, J. Magarian Blander, Giovanni Blandino, Klas Blomgren, Christoph Borner, Carl D. Bortner, Pierluigi Bove, Patricia Boya, Catherine Brenner, Petr Broz, Thomas Brunner, Rune Busk Damgaard, George A. Calin, Michelangelo Campanella, Eleonora Candi, Michele Carbone, Didac Carmona-Gutierrez, Francesco Cecconi, Francis K-M Chan, Guo-Qiang Chen, Quan Chen, Youhai H. Chen, Emily H. Cheng, Jerry E. Chipuk, John A. Cidlowski, Aaron Ciechanover, Gennaro Ciliberto, Marcus Conrad, Juan R. Cubillos-Ruiz, Peter E. Czabotar, Vincenzo D'Angiolella, Mads Daugaard, Ted M. Dawson, Valina L. Dawson, Ruggero De Maria, Bart De Strooper, Klaus-Michael Debatin, Ralph J. Deberardinis, Alexei Degterev, Giannino Del Sal, Mohanish Deshmukh, Francesco Di Virgilio, Marc Diederich, Scott J. Dixon, Brian D. Dynlacht, Wafik S. El-Deiry, John W. Elrod, Kurt Engeland, Gian Maria Fimia, Claudia Galassi, Carlo Ganini, Ana J. Garcia-Saez, Abhishek D. Garg, Carmen Garrido, Evripidis Gavathiotis, Motti Gerlic, Sourav Ghosh, Douglas R. Green, Lloyd A. Greene, Hinrich Gronemeyer, Georg Haecker, Gyorgy Hajnoczky, J. Marie Hardwick, Ygal Haupt, Sudan He, David M. Heery, Michael O. Hengartner, Claudio Hetz, David A. Hildeman, Hidenori Ichijo, Satoshi Inoue, Marja Jaeaettelae, Ana Janic, Bertrand Joseph, Philipp J. Jost, Thirumala-Devi Kanneganti, Michael Karin, Hamid Kashkar, Thomas Kaufmann, Gemma L. Kelly, Oliver Kepp, Adi Kimchi, Richard N. Kitsis, Daniel J. Klionsky, Ruth Kluck, Dmitri Krysko, Dagmar Kulms, Sharad Kumar, Sergio Lavandero, Inna N. Lavrik, John J. Lemasters, Gianmaria Liccardi, Andreas Linkermann, Stuart A. Lipton, Richard A. Lockshin, Carlos Lopez-Otin, Tom Luedde, Marion MacFarlane, Frank Madeo, Walter Malorni, Gwenola Manic, Roberto Mantovani, Saverio Marchi, Jean-Christophe Marine, Seamus J. Martin, Jean-Claude Martinou, Pier G. Mastroberardino, Jan Paul Medema, Patrick Mehlen, Pascal Meier, Gerry Melino, Sonia Melino, Edward A. Miao, Ute M. Moll, Cristina Munoz-Pinedo, Daniel J. Murphy, Maria Victoria Niklison-Chirou, Flavia Novelli, Gabriel Nunez, Andrew Oberst, Dimitry Ofengeim, Joseph T. Opferman, Moshe Oren, Michele Pagano, Theocharis Panaretakis, Manolis Pasparakis, Josef M. Penninger, Francesca Pentimalli, David M. Pereira, Shazib Pervaiz, Marcus E. Peter, Paolo Pinton, Giovanni Porta, Jochen H. M. Prehn, Hamsa Puthalakath, Gabriel A. Rabinovich, Krishnaraj Rajalingam, Kodi S. Ravichandran, Markus Rehm, Jean-Ehrland Ricci, Rosario Rizzuto, Nirmal Robinson, Cecilia M. P. Rodrigues, Barak Rotblat, Carla Rothlin, David C. Rubinsztein, Thomas Rudel, Alessandro Rufini, Kevin M. Ryan, Kristopher A. Sarosiek, Akira Sawa, Emre Sayan, Kate Schroder, Luca Scorrano, Federico Sesti, Feng Shao, Yufang Shi, Giuseppe S. Sica, John Silke, Hans-Uwe Simon, Antonella Sistigu, Anastasis Stephanou, Brent R. Stockwell, Flavie Strapazzon, Andreas Strasser, Liming Sun, Erwei Sun, Qiang Sun, Gyorgy Szabadkai, Stephen W. G. Tait, Daolin Tang, Nektarios Tavernarakis, Carol M. Troy, Boris Turk, Nicoletta Urbano, Peter Vandenabeele, Tom Vanden Berghe, Matthew G. Vander Heiden, Jacqueline L. Vanderluit, Alexei Verkhratsky, Andreas Villunger, Silvia von Karstedt, Anne K. Voss, Karen H. Vousden, Domagoj Vucic, Daniela Vuri, Erwin F. Wagner, Henning Walczak, David Wallach, Ruoning Wang, Ying Wang, Achim Weber, Will Wood, Takahiro Yamazaki, Huang-Tian Yang, Zahra Zakeri, Joanna E. Zawacka-Pankau, Lin Zhang, Haibing Zhang, Boris Zhivotovsky, Wenzhao Zhou, Mauro Piacentini, Guido Kroemer, Lorenzo Galluzzi
Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.
CELL DEATH AND DIFFERENTIATION
(2023)
Editorial Material
Biochemistry & Molecular Biology
Adam Wahida, Marcus Conrad
Summary: Ferroptosis is a prevalent and disease-relevant cell death mechanism caused by iron-dependent lipid peroxidation leading to membrane rupture. A recent study investigates how tension-sensing channels can regulate and modulate membrane tension in the context of ferroptotic cell death.
Editorial Material
Cell Biology
Eikan Mishima, Marcus Conrad
Summary: A recent study reveals that the metabolic enzyme creatinine kinase B (CKB) phosphorylates the protein GPX4, which could potentially affect the susceptibility of cancer cells to ferroptosis.
NATURE CELL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Eikan Mishima, Adam Wahida, Tobias Seibt, Marcus Conrad
Summary: Vitamin K plays a crucial role in various physiological processes, such as blood coagulation, by serving as a cofactor for protein conversion. It also has carboxylation-independent functions, acting as an electron carrier and preventing cell death. This perspective offers an overview of the diverse functions of vitamin K, including its involvement in ferroptosis, and discusses its relationship with ferroptosis suppressor protein-1. A comparison between vitamin K and ubiquinone from an evolutionary perspective may provide further insights.
Article
Biochemistry & Molecular Biology
Anuroop Venkateswaran Venkatasubramani, Toshiharu Ichinose, Mai Kanno, Ignasi Forne, Hiromu Tanimoto, Shahaf Peleg, Axel Imhof
Summary: Proteins involved in cellular metabolism and molecular regulation can extend lifespan in the laboratory, but their effect in real life depends on the ability to survive in non-ideal conditions. Loss of the acetyltransferase chameau (chm) in Drosophila melanogaster leads to increased healthy lifespan but decreased weight and starvation resistance, indicating a failure to regulate energy storage and expenditure. The ability to survive in environments with restricted food availability is a stronger evolutionary driver than the ability to live a long life, explaining why chm is still present in the organism's genome.
Letter
Multidisciplinary Sciences
Eikan Mishima, Toshitaka Nakamura, Jiashuo Zheng, Weijia Zhang, Andre Santos Dias Mourao, Peter Sennhenn, Marcus Conrad
Article
Multidisciplinary Sciences
Toshitaka Nakamura, Clara Hipp, Andre Santos Dias Mourao, Jan Borggraefe, Maceler Aldrovandi, Bernhard Henkelmann, Jonas Wanninger, Eikan Mishima, Elena Lytton, David Emler, Bettina Proneth, Michael Sattler, Marcus Conrad
Summary: Ferroptosis is a promising approach for treating difficult-to-treat tumors. The second ferroptosis-suppressing system, involving ferroptosis suppressor protein-1 (FSP1), has been identified, which efficiently prevents lipid peroxidation independently of the cyst(e)ine-glutathione (GSH)-glutathione peroxidase 4 (GPX4) axis. Through a small molecule library screen, the potent FSP1 inhibitors of 3-phenylquinazolinones were identified. These inhibitors trigger subcellular relocalization of FSP1 and induce FSP1 condensation, synergistically with GPX4 inhibition, leading to ferroptosis induction. The results suggest that targeting FSP1-dependent phase separation with icFSP1 could be an efficient anti-cancer therapy.
Review
Cell Biology
Bruno Galy, Marcus Conrad, Martina Muckenthaler
Summary: This review discusses the importance of iron in cellular functions and its tightly regulated mechanisms in mammals. Cells acquire, traffick, and export iron through various sensory and regulatory systems, and interact with systemic iron homeostasis control through multiple pathways. This knowledge is crucial for preventing diseases related to iron mismanagement.
NATURE REVIEWS MOLECULAR CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Vera Kleene, Valentina Corvaglia, Erika Chacin, Ignasi Forne, David B. Konrad, Pardis Khosravani, Celine Douat, Christoph F. Kurat, Ivan Huc, Axel Imhof
Summary: The use of synthetic foldamers that mimic double-stranded DNA has shown potential for interfering with protein-DNA interactions and disrupting the chromatin-bound proteome. These foldamers have been found to efficiently interfere with the association of the origin recognition complex with chromatin, leading to disruption of the cell cycle. This interaction is mediated by a direct interaction between the foldamers and the origin recognition complex, resulting in a failure to organize chromatin around replication origins.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Pediatrics
Richard Klaus, Teresa K. K. Barth, Axel Imhof, Franziska Thalmeier, Barbel Lange-Sperandio
Summary: This study assessed the influence of urine bag and clean catch collection methods on urinary proteomics in infants. The results showed that these two collection methods had minimal impact on urinary proteomics, with the biological characteristics of the urine samples being more important.
PEDIATRIC NEPHROLOGY
(2023)
Article
Chemistry, Multidisciplinary
Alexander Pichler, Markus Hillmeier, Matthias Heiss, Elsa Peev, Stylianos Xefteris, Barbara Steigenberger, Ines Thoma, Markus Mueller, Marco Borso, Axel Imhof, Thomas Carell
Summary: Queuosine is a highly complex hypermodified RNA nucleoside found in tRNAs. It has several derivatives, including glutamylated Queuosine (gluQ), which is only found in bacteria.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)