Review
Cell Biology
Saeko Aoyama-Ishiwatari, Yusuke Hirabayashi
Summary: Recent studies have shown that organelles do not exist in isolation, but form complex cooperative networks. Mitochondria-endoplasmic reticulum contact sites play crucial roles in regulating various biochemical and signaling functions within cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Clinical Neurology
Dajana Grossmann, Nina Malburg, Hannes Glass, Veronika Weeren, Verena Sondermann, Julia F. F. Pfeiffer, Janine Petters, Jan Lukas, Philip Seibler, Christine Klein, Anne Gruenewald, Andreas Hermann
Summary: Recent studies have shown that PINK1 and Parkin play a crucial role in mitochondrial calcium homeostasis and regulation of MERCSs. Using iPSC-derived dopaminergic neurons, researchers found that deficiency in PINK1 or PRKN affects MERCSs dynamics and composition, leading to impaired calcium homeostasis. These findings provide insights into the pathogenesis of PINK1/Parkin-related Parkinson's disease.
MOVEMENT DISORDERS
(2023)
Article
Cell Biology
Laura Lopez-Molina, Joaquin Fernandez-Irigoyen, Carmen Cifuentes-Diaz, Jordi Alberch, Jean-Antoine Girault, Enrique Santamaria, Silvia Gines, Albert Giralt
Summary: This study explores the function of Pyk2 in mitochondria-associated membranes (MAMs) and demonstrates its role in regulating ER-mitochondria calcium efflux, affecting mitochondrial function and leading to calcium homeostasis imbalance.
Article
Clinical Neurology
Eduardo Benarroch
Summary: Cells rely on membrane-bound organelles for their normal function and survival. These organelles interact with each other through membrane contact sites, enabling their cross-talk and cooperation for cellular homeostasis. The membrane contact sites are critical for lipid and calcium transfer, cell metabolism, and regulation of organelle dynamics. Dysfunction of organelle cross-talk is emerging as an important mechanism in neurodegenerative disorders, suggesting that targeting organelle contact sites could be a potential therapeutic approach.
Article
Biology
Yelena Sargsyan, Uta Bickmeyer, Christine S. Gibhardt, Katrin Streckfuss-Bomeke, Ivan Bogeski, Sven Thoms
Summary: Peroxisomes in HeLa cells and cardiomyocytes are able to uptake calcium and are tightly interconnected with cytosolic calcium signals. Cardiac peroxisomes can uptake calcium on a beat-to-beat basis, indicating a potential role in shaping cellular calcium dynamics of cardiomyocytes.
LIFE SCIENCE ALLIANCE
(2021)
Correction
Biochemistry & Molecular Biology
Emma Louise Wilson, Emmanouil Metzakopian
Summary: A correction to this paper has been published.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Physiology
Jing Zhang, Feng Zhang, Yanou Wang
Summary: Diabetic cardiomyopathy is associated with mitochondrial damage, specifically due to increased mitochondria-endoplasmic reticulum (ER) contact. Hyperglycemia induces this contact in cardiomyocytes, but silencing of Mfn2 can protect against mitochondrial dysfunction, calcium overload, apoptosis, and ER stress, enhancing cardiomyocyte survival under high-glucose conditions.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Cell Biology
Amit S. Joshi
Summary: Peroxisomes are vital organelles in cells, generated and maintained through membrane contacts with other organelles, playing a crucial role in normal cellular function.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Maria Livia Sassano, Blanca Felipe-Abrio, Patrizia Agostinis
Summary: Membrane contact sites (MCS) between organelles are crucial for the structural integrity and homeostasis of eukaryotic cells, facilitating intracellular signaling and exchange of ions, metabolites, and lipids. In particular, ER-mitochondria contacts (EMCS) play a key role in regulating lipid composition, physiological functions, and lipid-mediated signaling pathways, with disruptions potentially favoring key traits of cancer cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Veijo T. Salo
Summary: Cells store excess energy in lipid droplets (LDs), and the lipodystrophy protein seipin plays a crucial role in LD biogenesis and ER-LD contact site maintenance. Recent studies have provided insights into the molecular function of seipin as a LD nucleator in early LD biogenesis and its potential involvement in ER-mitochondria contact sites and calcium metabolism. This minireview discusses these recent findings.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Review
Cell Biology
Chenlu Li, Tiantian Qian, Ruyue He, Chun Wan, Yinghui Liu, Haijia Yu
Summary: Endoplasmic reticulum (ER) forms direct membrane contact sites with the plasma membrane (PM) in eukaryotic cells, playing crucial roles in lipid homeostasis, ion dynamics, and cell signaling through protein-protein or protein-lipid interactions. Distinct tethering factors dynamically regulate the architecture of ER-PM junctions in response to signals, and the physiological roles of these contact sites rely on various regulators acting in diverse cellular processes. This review focuses on proteins at ER-PM contact sites, highlighting recent progress in their mechanisms and physiological roles.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Mahlegha Ghavami, Gregory D. Fairn
Summary: This minireview discusses the functions of ER-phagosome contact sites in the process of phagocytosis, from the early stages of particle engulfment to the dissolution of phagolysosome into lysosomes. It also highlights the aspects of ER-phagosome contact sites that require further exploration.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Michiko Shirane, Hiroyuki Kamiguchi
Summary: Axon growth and guidance in the developing nervous system rely on intracellular membrane dynamics that involve endosome maturation and transport, as well as its regulated tethering to the endoplasmic reticulum (ER). Recent studies have identified several key molecules, such as protrudin, which plays a dynamic role at membrane contact sites between the ER and endosomes/lysosomes, and myosin Va, which acts as a sensor for ER-derived Ca2+ that triggers peri-ER membrane export. These molecules form different types of multiprotein complexes at the interface of organelles and, in response to their surrounding microenvironments, such as Ca2+ concentrations and lipid contents, regulate the directional movement of endosomal vesicles in extending axons. Here, we review the molecular mechanisms underlying membrane dynamics and inter-organelle interactions during neuronal morphogenesis.
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Dong-Oh Moon
Summary: This review provides a comprehensive analysis of the multifaceted role of calcium in apoptosis regulation, focusing on its associated signaling pathways and molecular mechanisms. It explores the impact of calcium on apoptosis through its effects on various cellular compartments and highlights its connection to ER stress. Additionally, it discusses the interplay between calcium and proteins such as calpains, calmodulin, and Bcl-2 family members, and its role in regulating caspase activation and pro-apoptotic factor release. Understanding the complex relationship between calcium and apoptosis is crucial for identifying potential treatment options for diseases associated with imbalanced cell death.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Aurora Gil-Hernandez, Miguel Arroyo-Campuzano, Arturo Simoni-Nieves, Cecilia Zazueta, Luis Enrique Gomez-Quiroz, Alejandro Silva-Palacios
Summary: Membrane contact sites (MCS) are defined as areas of proximity between heterologous or homologous membranes characterized by specific proteins, playing a crucial role in regulating physiological processes such as apoptosis, calcium, and lipid signaling. Recent studies have highlighted the significance of MCS in cancer cells, particularly in calcium and lipid signaling, as well as their role in tumor progression, which may have implications for cancer biology research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Mandy B. Hulst, Thadee Grocholski, Jacques J. C. Neefjes, Gilles P. van Wezel, Mikko Metsa-Ketela
Summary: Doxorubicin, widely used in cancer treatment but limited by its severe side-effects, may be surpassed by new anthracycline-based drugs that focus on histone eviction activity to avoid cardiac toxicity. Recent advancements in biosynthesis and discovery of new congeners from rare Actinobacteria have laid the foundation for the development of novel anthracyclines.
NATURAL PRODUCT REPORTS
(2022)
Article
Oncology
Thomas P. Brouwer, Sabina Y. van der Zanden, Manon van der Ploeg, Jaap D. H. van Eendenburg, Bert A. Bonsing, Noel F. C. C. de Miranda, Jacques J. Neefjes, Alexander L. Vahrmeijer
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal type of cancer with limited treatment options. This study investigated the effectiveness of anthracyclines and standard-of-care drugs against PDAC cell lines. The results showed that aclarubicin had superior antitumor activity compared to other drugs. Combination treatment with gemcitabine and aclarubicin exhibited a synergistic effect. Aclarubicin induced apoptosis in all PDAC cell lines. These findings suggest that aclarubicin should be reconsidered as a potential treatment option for pancreatic cancer patients.
Article
Oncology
Yumeng Wang, Sabina Y. van der Zanden, Suzanne van Leerdam, Mayke M. H. Tersteeg, Anneke Kastelein, Stephan Michel, Jacques Neefjes, Johanna H. Meijer, Tom Deboer
Summary: Cancer-related fatigue (CRF) is a devastating long-term side effect that greatly affects the quality of life of cancer survivors. This study suggests that CRF may be caused by a dysfunctioning circadian clock, rather than changes in sleep. Additionally, the type of chemotherapy provided can influence the development of CRF. These findings have implications for selecting and improving chemotherapy to prevent CRF in cancer treatment.
Review
Cell Biology
Sabina Y. van der Zanden, Marlieke L. M. Jongsma, Anna C. M. Neefjes, Ilana Berlin, Jacques Neefjes
Summary: The nuclear envelope plays a crucial role in eukaryotic cells as a physical barrier and gate-keeper for selective transport between the nucleus and cytoplasm. During open mitosis, the nuclear envelope fragments to allow spindle formation and chromosome segregation, leading to mixing of nuclear and cytoplasmic soluble fractions. Recent studies have revealed the mechanisms behind the restoration of soluble proteome homeostasis following nuclear envelope reformation in daughter cells. This article provides an overview of how mitotic cells overcome this challenge to ensure continuity of cellular functions and discusses its implications for the proteasome, which functions in both the cytoplasmic and nuclear compartments.
TRENDS IN CELL BIOLOGY
(2023)
Article
Immunology
Ruud H. Wijdeven, Birol Cabukusta, Felix M. Behr, Xueer Qiu, Deeba Amiri, Daniel M. Borras, Ramon Arens, Yun Liang, Jacques Neefjes
Summary: The PD-L1/2-PD-1 immune checkpoint is crucial for maintaining peripheral tolerance and preventing autoimmunity, but tumor cells can exploit it for immune evasion. This study identified three factors, GATA2, MBD6, and VGLL3, that upregulate PD-L1 expression. VGLL3 acts as a transcriptional regulator and, in conjunction with TEAD1 and RUNXI/3, drives the expression of PD-L1/2. This work reveals a new transcriptional complex controlling PD-L1/2 expression and suggests that VGLL3 can balance inflammation by upregulating the anti-inflammatory factors PD-L1 and PD-L2.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Immunology
Fiamma Berner, David Bomze, Christa Lichtensteiger, Vincent Walter, Rebekka Niederer, Omar Hasan Ali, Nina Wyss, Jens Bauer, Lena Katharina Freudenmann, Ana Marcu, Eva-Maria Wolfschmitt, Sebastian Haen, Thorben Gross, Marie-Therese Abdou, Stefan Diem, Stella Knopefli, Tobias Sinnberg, Kathrin Hofmeister, Hung-Wei Cheng, Marieta Toma, Niklas Kluemper, Mette-Triin Purde, Oltin Tiberiu Pop, Ann-Kristin Jochum, Steve Pascolo, Markus Joerger, Martin Frueh, Wolfram Jochum, Hans-Georg Rammensee, Heinz Laeubli, Michael Hoelzel, Jacques Neefjes, Juliane Walz, Lukas Flatz
Summary: This study successfully identified self-antigens that likely mediate effective antitumor T cell responses in non-small cell lung cancer (NSCLC) using the DITAS method. Napsin A was identified as a self-antigen that elicited strong CD8(+) T cell responses. These findings may contribute to understanding the immune-related adverse events induced by immune checkpoint blockade therapy.
SCIENCE IMMUNOLOGY
(2022)
Review
Cell Biology
Marlieke L. M. Jongsma, Nina Bakker, Jacques Neefjes
Summary: The endosomal system coordinates the transport of substances within cells, and its motion is regulated by microtubule-based motor proteins. These interactions determine the mobility of the endosomes.
JOURNAL OF CELL SCIENCE
(2023)
Article
Biology
Angelo Ferreira Chora, Dora Pedroso, Eleni Kyriakou, Nadja Pejanovic, Henrique Colaco, Raffaella Gozzelino, Andre Barros, Katharina Willmann, Tiago Velho, Catarina F. Moita, Isa Santos, Pedro Pereira, Silvia Carvalho, Filipa Batalha Martins, Joao A. Ferreira, Sergio Fernandes de Almeida, Vladimir Benes, Josef Anrather, Sebastian Weis, Miguel P. Soares, Arie Geerlof, Jacques Neefjes, Michael Sattler, Ana C. Messias, Ana Neves-Costa, Luis Ferreira Moita, Yousef Abu-Amer
Summary: Anthracyclines, a class of commonly used and effective anticancer drugs, were found to decrease the transcription of NF-kappa B-dependent gene targets and disturb the complexes formed between NF-kappa B subunit RelA and its DNA-binding sites. The anthracycline variants without inducing DNA damage also suppressed inflammation, which has implications for cancer therapy and the development of anti-inflammatory drugs with limited side effects.
Article
Cell Biology
Daphne M. van Elsland, Janneke W. Duijster, Jilei Zhang, Virginie Stevenin, Yongguo Zhang, Lang Zha, Yinglin Xia, Eelco Franz, Jun Sun, Lapo Mughini-Gras, Jacques Neefjes
Summary: Salmonella infection disrupts cellular integrity and may induce oncogenic transformation. Systemic S. Typhi infection is associated with gallbladder cancer, while severe non-typhoidal Salmonella infection is associated with colon cancer. A serological study found a significant positive correlation between exposure to non-typhoidal Salmonella and colon cancer risk.
CELL REPORTS MEDICINE
(2022)
Review
Cell Biology
Ilana Berlin, Aysegul Sapmaz, Virginie Stevenin, Jacques Neefjes
Summary: The endolysosomal system is a dynamic network of vesicles that sense and interpret environmental cues, leading to homeostasis. To integrate extracellular signals with intracellular processes, endosomes and lysosomes make decisions on fusion or fission, recycling or degradation, and transport or contact with other organelles. These decisions are regulated by reversible post-translational modifications (PTMs) involving ubiquitin (Ub) and ubiquitin-like (Ubl) proteins. This ubiquitylation cycle controls protein stability and behavior on the endolysosomal membranes, fine-tuning macromolecular complex assembly and function. Additionally, this system is exploited by intracellular bacteria to hijack host trafficking pathways for their own benefit.
JOURNAL OF CELL SCIENCE
(2023)
Article
Oncology
Maaike Y. Kapteijn, Shanna Zwaan, Esther ter Linden, El Houari Laghmani, Rob F. P. van den Akker, Araci M. R. Rondon, Sabina Y. van der Zanden, Jacques Neefjes, Henri H. Versteeg, Jeroen T. Buijs
Summary: This study found a promoting role of the commonly used chemotherapeutic agents Temozolomide and Lomustine on tissue factor (TF) procoagulant activity and gene/protein expression in glioblastoma (GBM) cell lines. This may explain the increased risk of thrombosis in GBM patients undergoing chemotherapy. Therefore, GBM patients with high TF levels may benefit from anticoagulant treatment to decrease the risk of chemotherapy-induced thrombosis.
Article
Biochemistry & Molecular Biology
Tom Cremer, Lenard M. Voortman, Erik Bos, Marlieke L. M. Jongsma, Laurens R. ter Haar, Jimmy J. L. L. Akkermans, Cami M. P. Talavera Ormeno, Ruud H. M. Wijdeven, Jelle de Vries, Robbert Q. Kim, George M. C. Janssen, Peter A. van Veelen, Roman Koning, Jacques Neefjes, Ilana Berlin
Summary: Proteotoxic stress triggers remodeling of the endoplasmic reticulum (ER) membrane, resulting in the formation of a perinuclear quality control compartment (ERQC) for the degradation of misfolded proteins. Vimentin intermediate filaments act as anchors, recruiting the RING finger protein 26 (RNF26) to the perinuclear ER subdomains and facilitating the spatial retention of endolysosomes. RNF26 and vimentin are both essential for the formation of the perinuclear ERQC and its association with proteolytic compartments, allowing efficient recovery from ER stress via the Sec62-mediated ER-phagy pathway.
Meeting Abstract
Oncology
Erika Fletcher, Iliana Kerzeli, Robert Cordfunke, Aikaterini Nasi, Gunilla Tornqvist, Robert Valentijn, Frida Lindqvist, Inken Dillmann, Martin Lord, Neanke Bouwman, Jacques Neefjes, Natasja Dolezal, Kees Franken, Stephanie McArdle, Murrium Ahmad, Silvia Johansson, Ferry Ossendorp, Michael Haggman, Wolfgang Lilleby, Gustav Ullenhag, Sam Ladjevardi, Justyna Jarblad, Jan Wouter Drijfhout, Sara Mangsbo
Review
Biochemistry & Molecular Biology
Virginie Stevenin, Jacques Neefjes
Summary: Intracellular bacteria have developed mechanisms to influence host protein post-translational modifications (PTMs) to their advantage. Recent discoveries on host PTMs shed light on the complex host-pathogen interaction. These insights may contribute to the development of new therapeutic approaches.
CELL CHEMICAL BIOLOGY
(2022)
