The biology of Lonp1: More than a mitochondrial protease.
Abstract Initially discovered as a protease responsible for degradation of misfolded or damaged proteins, the mitochondrial Lon protease (Lonp1) turned out to be a multifaceted enzyme, that displays at least three different functions (proteolysis, chaperone activity, binding of mtDNA) and that finely regulates several cellular processes, within and without mitochondria. Indeed, LONP1 in humans is ubiquitously expressed, and is involved in regulation of response to oxidative stress and, heat shock, in the maintenance of mtDNA, in the regulation of mitophagy. Furthermore, its proteolytic activity can regulate severa...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Gibellini L, De Gaetano A, Mandrioli M, Van Tongeren E, Bortolotti CA, Cossarizza A, Pinti M Tags: Int Rev Cell Mol Biol Source Type: research

Links between cancer metabolism and cisplatin resistance.
Abstract Cisplatin is one of the most potent and widely used chemotherapeutic agent in the treatment of several solid tumors, despite the high toxicity and the frequent relapse of patients due to the onset of drug resistance. Resistance to chemotherapeutic agents, either intrinsic or acquired, is currently one of the major problems in oncology. Thus, understanding the biology of chemoresistance is fundamental in order to overcome this challenge and to improve the survival rate of patients. Studies over the last 30 decades have underlined how resistance is a multifactorial phenomenon not yet completely understood. ...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Cocetta V, Ragazzi E, Montopoli M Tags: Int Rev Cell Mol Biol Source Type: research

New emerging roles of Polycystin-2 in the regulation of autophagy.
llo A Abstract Polycystin-2 (PC2) is a calcium channel that can be found in the endoplasmic reticulum, the plasmatic membrane, and the primary cilium. The structure of PC2 is characterized by a highly ordered C-terminal tail with an EF-motif (calcium-binding domain) and a canonical coiled-coil domain (CCD; interaction domain), and its activity is regulated by interacting partners and post-translational modifications. Calcium mobilization into the cytosol by PC2 has been mainly associated with cell growth and differentiation, and therefore mutations or dysfunction of PC2 lead to renal and cardiac consequences. Inte...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Peña-Oyarzun D, Batista-Gonzalez A, Kretschmar C, Burgos P, Lavandero S, Morselli E, Criollo A Tags: Int Rev Cell Mol Biol Source Type: research

Pharmacological methods to transcriptionally modulate double-strand break DNA repair.
Abstract There is much interest in targeting DNA repair pathways for use in cancer therapy, as the effectiveness of many therapeutic agents relies on their ability to cause damage to DNA, and deficiencies in DSB repair pathways can make cells more sensitive to specific cancer therapies. For example, defects in the double-strand break (DSB) pathways, non-homologous end joining (NHEJ) and homology-directed repair (HDR), induce sensitivity to radiation therapy and poly(ADP)-ribose polymerase (PARP) inhibitors, respectively. However, traditional approaches to inhibit DNA repair through small molecule inhibitors have o...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Kaplan AR, Glazer PM Tags: Int Rev Cell Mol Biol Source Type: research

Evolutionary insights into the aphid genome: Aphid genomics between quality problems and intriguing perspectives.
Abstract In the last decade the genomes of several aphid species have been sequenced allowing a better understanding of their biology and evolution. Unfortunately, as frequently occurs with the next generation sequencing technologies, several aphid genomes consist in fragmented assemblies that contain thousands of genomic scaffolds of reduced length. In order to improve the quality of the published genomic data, several research groups are currently resequencing aphid DNA making possible to take the full advantage of genomics to face complex biological problems, such as aphid diversification. This review is aimed ...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Mandrioli M, Manicardi GC Tags: Int Rev Cell Mol Biol Source Type: research

Stratifying nutritional restriction in cancer therapy: Next stop, personalized medicine.
Abstract Dietary interventions combined with cancer drugs represent a clinically valid polytherapy. In particular nutrient restriction (NR) in the form of varied fasting or caloric restriction regimens holds great clinical promise, conceptually due to the voracious anabolic appetite of cancer cells. This metabolic dependency is driven by a strong selective pressure to increasingly acquire biomass of a proliferating tumor and can be therapeutically exploited as vulnerability. A host of preclinical data suggest that NR can potentiate the efficacy of, or alleviate resistance to, cancer drugs. However, complicating cl...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Krstic J, Pieber TR, Prokesch A Tags: Int Rev Cell Mol Biol Source Type: research

The biology of vascular calcification.
Abstract Vascular calcification (VC), characterized by different mineral deposits (i.e., carbonate apatite, whitlockite and hydroxyapatite) accumulating in blood vessels and valves, represents a relevant pathological process for the aging population and a life-threatening complication in acquired and in genetic diseases. Similarly to bone remodeling, VC is an actively regulated process in which many cells and molecules play a pivotal role. This review aims at: (i) describing the role of resident and circulating cells, of the extracellular environment and of positive and negative factors in driving the mineralizati...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Daniela Q, Federica B, Lofaro FD Tags: Int Rev Cell Mol Biol Source Type: research

Molecular mechanisms of selective autophagy in Drosophila.
Abstract Autophagy is a highly conserved catabolic process in which cytoplasmic material is recycled under various conditions of cellular stress, preventing cell damage and promoting survival in the event of energy or nutrient shortage, or in response to various cytotoxic insults. Autophagy is also responsible for the removal of aggregated proteins and damaged organelles, playing a vital role in the quality control of proteins and organelles. Impairment of autophagy has been linked to various diseases, including cancer and neurodegenerative disorders, making it a very interesting process for further research. Rece...
Source: International Review of Cell and Molecular Biology - June 3, 2020 Category: Cytology Authors: Gohel R, Kournoutis A, Petridi S, Nezis IP Tags: Int Rev Cell Mol Biol Source Type: research

Poly (ADP-ribose) (PAR)-dependent cell death in neurodegenerative diseases.
Abstract Disruption of cellular functions with aging-induced accumulation of neuronal stressors causes cell death which is a common feature of neurodegenerative diseases. Studies in a variety of neurodegenerative disease models demonstrate that poly (ADP-ribose) (PAR)-dependent cell death, also named parthanatos, is responsible for neuronal loss in neurological diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). Parthanatos has distinct features that differ from caspase-dependent apoptosis, necrosis or autophagic cell death. Parth...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Park H, Kam TI, Dawson TM, Dawson VL Tags: Int Rev Cell Mol Biol Source Type: research

Regulation of cell death in the cardiovascular system.
Abstract The adult heart is a post-mitotic terminally differentiated organ; therefore, beyond development, cardiomyocyte cell death is maladaptive. Heart disease is the leading cause of death in the world and aberrant cardiomyocyte cell death is the underlying problem for most cardiovascular-related diseases and fatalities. In this chapter, we will discuss the different cell death mechanisms that engage during normal cardiac development, aging, and disease states. The most abundant loss of cardiomyocytes occurs during a myocardial infarction, when the blood supply to the heart is obstructed, and the affected myoca...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Patel P, Karch J Tags: Int Rev Cell Mol Biol Source Type: research

The involvement of regulated cell death forms in modulating the bacterial and viral pathogenesis.
Abstract Apoptosis, necroptosis and pyroptosis represent three distinct types of regulated cell death forms, which play significant roles in response to viral and bacterial infections. Whereas apoptosis is characterized by cell shrinkage, nuclear condensation, bleb formation and retained membrane integrity, necroptosis and pyroptosis exhibit osmotic imbalance driven cytoplasmic swelling and early membrane damage. These three cell death forms exert distinct immune stimulatory potential. The caspase driven apoptotic cell demise is considered in many circumstances as anti-inflammatory, whereas the two lytic cell deat...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Imre G Tags: Int Rev Cell Mol Biol Source Type: research

A connection in life and death: The BCL-2 family coordinates mitochondrial network dynamics and stem cell fate.
Abstract The B cell CLL/lymphoma-2 (BCL-2) family of proteins control the mitochondrial pathway of apoptosis, also known as intrinsic apoptosis. Direct binding between members of the BCL-2 family regulates mitochondrial outer membrane permeabilization (MOMP) after an apoptotic insult. The ability of the cell to sense stress and translate it into a death signal has been a major theme of research for nearly three decades; however, other mechanisms by which the BCL-2 family coordinates cellular homeostasis beyond its role in initiating apoptosis are emerging. One developing area of research is understanding how the B...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Rasmussen ML, Gama V Tags: Int Rev Cell Mol Biol Source Type: research

Molecular mechanisms of necroptosis and relevance for neurodegenerative diseases.
s CMP Abstract Necroptosis is a regulated cell death pathway morphologically similar to necrosis that depends on the kinase activity of receptor interacting protein 3 (RIP3) and the subsequent activation of the pseudokinase mixed lineage kinase domain-like protein (MLKL), being also generally dependent on RIP1 kinase activity. Necroptosis can be recruited during pathological conditions, usually following the activation of death receptors under specific cellular contexts. In this regard, necroptosis has been implicated in the pathogenesis of multiple disorders, including acute and chronic neurodegenerative diseases...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Dionísio PA, Amaral JD, Rodrigues CMP Tags: Int Rev Cell Mol Biol Source Type: research

Necroptosis, ADAM proteases and intestinal (dys)function.
Abstract Recently, an unexpected connection between necroptosis and members of the a disintegrin and metalloproteinase (ADAM) protease family has been reported. Necroptosis represents an important cell death routine which helps to protect from viral, bacterial, fungal and parasitic infections, maintains adult T cell homeostasis and contributes to the elimination of potentially defective organisms before parturition. Equally important for organismal homeostasis, ADAM proteases control cellular processes such as development and differentiation, immune responses or tissue regeneration. Notably, necroptosis as well as...
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Heib M, Rose-John S, Adam D Tags: Int Rev Cell Mol Biol Source Type: research

Preface: Life through death-Key role of cellular suicide for colonial and organismal homeostasis.
PMID: 32381180 [PubMed - in process] (Source: International Review of Cell and Molecular Biology)
Source: International Review of Cell and Molecular Biology - May 9, 2020 Category: Cytology Authors: Spetz J, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

The mechanisms and cell signaling pathways of programmed cell death in the bacterial world.
Abstract While programmed cell death was once thought to be exclusive to eukaryotic cells, there are now abundant examples of well regulated cell death mechanisms in bacteria. The mechanisms by which bacteria undergo programmed cell death are diverse, and range from the use of toxin-antitoxin systems, to prophage-driven cell lysis. Moreover, some bacteria have learned how to coopt programmed cell death systems in competing bacteria. Interestingly, many of the potential reasons as to why bacteria undergo programmed cell death may parallel those observed in eukaryotic cells, and may be altruistic in nature. These in...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Smith RP, Barraza I, Quinn RJ, Fortoul MC Tags: Int Rev Cell Mol Biol Source Type: research

Crosstalk between apoptosis and autophagy signaling pathways.
Abstract The fate of a cell is determined by multiple signaling pathways in response to a range of stimuli. Probably the most prominent cell death mechanism is apoptosis which can be triggered by both internal stresses, as well as extracellular stimuli, and is executed by two well-characterized pathways, the intrinsic and the extrinsic apoptosis pathways. Although autophagy can also lead to cell death under certain circumstances, its major function is as a cell survival process. Given that the life of a cell is at stake, it is not surprising that there is significant molecular crosstalk between these pathways. The...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Fairlie WD, Tran S, Lee EF Tags: Int Rev Cell Mol Biol Source Type: research

The interplay of autophagy and non-apoptotic cell death pathways.
Abstract Autophagy, the process of macromolecular degradation through the lysosome, has been extensively studied for the past decade or two. Autophagy can regulate cell death, especially apoptosis, through selective degradation of both positive and negative apoptosis regulators. However, multiple other programmed cell death pathways exist. As knowledge of these other types of cell death expand, it has been suggested that they also interact with autophagy. In this review, we discuss the molecular mechanisms that comprise three non-apoptotic forms of cell death (necroptosis, pyroptosis and ferroptosis) focusing on h...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Miller DR, Cramer SD, Thorburn A Tags: Int Rev Cell Mol Biol Source Type: research

Redox signaling in the pathogenesis of human disease and the regulatory role of autophagy.
Abstract Aberrant cell death signaling and oxidative stress are implicated in myriad of human pathological states such as neurodegenerative, cardiovascular, metabolic and liver diseases, as well as drug-induced toxicities. While regulated cell death and mild oxidative stress are essential during normal tissue homeostasis, deregulated signaling can trigger massive depletion in a particular cell type and/or damage tissues and impair organ function with deleterious consequences that manifest as disease states. If regeneration cannot restore tissue homeostasis, the severity of the disease correlates with the extent of...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Pervaiz S, Bellot GL, Lemoine A, Brenner C Tags: Int Rev Cell Mol Biol Source Type: research

Transcriptional and epigenetic control of regulated cell death in yeast.
Abstract Unicellular organisms like yeast can undergo controlled demise in a manner that is partly reminiscent of mammalian cell death. This is true at the levels of both mechanistic and functional conservation. Yeast offers the combination of unparalleled genetic amenability and a comparatively simple biology to understand both the regulation and evolution of cell death. In this minireview, we address the capacity of the nucleus as a regulatory hub during yeast regulated cell death (RCD), which is becoming an increasingly central question in yeast RCD research. In particular, we explore and critically discuss the...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Zimmermann A, Tadic J, Kainz K, Hofer SJ, Bauer MA, Carmona-Gutierrez D, Madeo F Tags: Int Rev Cell Mol Biol Source Type: research

Cell death in the avian brain with emphasis on the development and plasticity of the song control system.
Abstract Programmed cell death is a fundamental feature of brain development, homeostasis, and adult plasticity. One model system, in which the role of cell death in establishment, maintenance and plasticity of neural tissues is evident throughout both early development and in the adult, is the neural circuitry underlying the learning and production of singing behavior in songbirds. The dramatic sexual dimorphism and natural, cyclical growth and regression of the song control system provides a useful environment for studying programmed cell death. Especially valuable and unique to songbirds, the occurrence of cell...
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Larson TA Tags: Int Rev Cell Mol Biol Source Type: research

Preface: Life through death-Key role of cellular suicide for colonial and organismal homeostasis.
PMID: 32334819 [PubMed - in process] (Source: International Review of Cell and Molecular Biology)
Source: International Review of Cell and Molecular Biology - April 28, 2020 Category: Cytology Authors: Spetz J, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

Bcl-2 family proteins, beyond the veil.
Abstract Apoptosis is an important part of both health and disease and is often regulated by the BCL-2 family of proteins. These proteins are either pro- or anti-apoptotic, existing in a delicate balance during homeostasis. They are best known for their role in regulating the activation of caspases and the execution of a cell in response to a variety of stimuli. However, it is often forgotten that these BCL-2 family proteins also have important roles to play in cell maintenance that are not associated with apoptosis. These include roles in regulating processes such as cell cycle progression, mitochondrial function...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Glab JA, Cao Z, Puthalakath H Tags: Int Rev Cell Mol Biol Source Type: research

Type 3 IP3 receptors: The chameleon in cancer.
Abstract Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs), intracellular calcium (Ca2+) release channels, fulfill key functions in cell death and survival processes, whose dysregulation contributes to oncogenesis. This is essentially due to the presence of IP3Rs in microdomains of the endoplasmic reticulum (ER) in close proximity to the mitochondria. As such, IP3Rs enable efficient Ca2+ transfers from the ER to the mitochondria, thus regulating metabolism and cell fate. This review focuses on one of the three IP3R isoforms, the type 3 IP3R (IP3R3), which is linked to proapoptotic ER-mitochondrial Ca2+ transfer...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Rosa N, Sneyers F, Parys JB, Bultynck G Tags: Int Rev Cell Mol Biol Source Type: research

On the role of sphingolipids in cell survival and death.
Abstract Sphingolipids, universal components of biological membranes of all eukaryotic organisms, from yeasts to mammals, in addition of playing a structural role, also play an important part of signal transduction pathways. They participate or, also, ignite several fundamental subcellular signaling processes but, more in general, they directly contribute to key biological activities such as cell motility, growth, senescence, differentiation as well as cell fate, i.e., survival or death. The sphingolipid metabolic pathway displays an intricate network of reactions that result in the formation of multiple sphingoli...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Iessi E, Marconi M, Manganelli V, Sorice M, Malorni W, Garofalo T, Matarrese P Tags: Int Rev Cell Mol Biol Source Type: research

A lipid perspective on regulated cell death.
acute;ez AJ Abstract Lipids are fundamental to life as structural components of cellular membranes and for signaling. They are also key regulators of different cellular processes such as cell division, proliferation, and death. Regulated cell death (RCD) requires the engagement of lipids and lipid metabolism for the initiation and execution of its killing machinery. The permeabilization of lipid membranes is a hallmark of RCD that involves, for each kind of cell death, a unique lipid profile. While the permeabilization of the mitochondrial outer membrane allows the release of apoptotic factors to the cytosol durin...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Flores-Romero H, Ros U, García-Sáez AJ Tags: Int Rev Cell Mol Biol Source Type: research

Mcl-1 as a "barrier" in cancer treatment: Can we target it now?
Mcl-1 as a "barrier" in cancer treatment: Can we target it now? Int Rev Cell Mol Biol. 2020;351:23-55 Authors: Pervushin NV, Senichkin VV, Zhivotovsky B, Kopeina GS Abstract During the last two decades, the study of Mcl-1, an anti-apoptotic member of the Bcl-2 family, attracted researchers due to its important role in cancer cell survival and tumor development. The significance of Mcl-1 protein in resistance to chemotherapeutics makes it an attractive target in cancer therapy. Here, we discuss the diverse possibilities for indirect Mcl-1 inhibition through its downregulation, for example, vi...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Pervushin NV, Senichkin VV, Zhivotovsky B, Kopeina GS Tags: Int Rev Cell Mol Biol Source Type: research

TRAIL receptor signaling: From the basics of canonical signal transduction toward its entanglement with ER stress and the unfolded protein response.
m M Abstract The cytokine tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the large TNF superfamily that can trigger apoptosis in transformed or infected cells by binding and activating two receptors, TRAIL receptor 1 (TRAILR1) and TRAIL receptor 2 (TRAILR2). Compared to other death ligands of the same family, TRAIL induces apoptosis preferentially in malignant cells while sparing normal tissue and has therefore been extensively investigated for its suitability as an anti-cancer agent. Recently, it was noticed that TRAIL receptor signaling is also linked to endoplasmic reticulu...
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Stöhr D, Jeltsch A, Rehm M Tags: Int Rev Cell Mol Biol Source Type: research

Preface: Life through death-Key role of cellular suicide for colonial and organismal homeostasis.
PMID: 32247583 [PubMed - in process] (Source: International Review of Cell and Molecular Biology)
Source: International Review of Cell and Molecular Biology - April 7, 2020 Category: Cytology Authors: Spetz J, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

Dendritic cell subsets and locations.
Abstract Dendritic cells (DCs) are a unique class of immune cells that act as a bridge between innate and adaptive immunity. The discovery of DCs by Cohen and Steinman in 1973 laid the foundation for DC biology, and the advances in the field identified different versions of DCs with unique properties and functions. DCs originate from hematopoietic stem cells, and their differentiation is modulated by Flt3L. They are professional antigen-presenting cells that patrol the environmental interphase, sites of infection, or infiltrate pathological tissues looking for antigens that can be used to activate effector cells. ...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Balan S, Saxena M, Bhardwaj N Tags: Int Rev Cell Mol Biol Source Type: research

The role of dendritic cells in cancer.
Abstract Cancer immunotherapy harnesses the ability of the immune system to recognize and eliminate cancer. The potent ability of dendritic cells (DCs) to initiate and regulate adaptive immune responses underpins the successful generation of anti-tumor immune responses. DCs are a heterogeneous leukocyte population comprised of distinct subsets that drive specific types of immune responses. Understanding how DCs induce tumor immune responses and the mechanisms adopted by tumors to evade DC surveillance is essential to render immunotherapies more effective. This review discusses current knowledge of the roles played...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Lee YS, Radford KJ Tags: Int Rev Cell Mol Biol Source Type: research

Interplay between dendritic cells and cancer cells.
Abstract Dendritic cells (DCs) orchestrate a repertoire of immune responses that bring about resistance to infection and tolerance to self. Cancers can exploit DCs to evade immunity, but DCs also can generate resistance to cancer. Owing to their capacity to capture, process, and present antigens to naïve T cells, thereby launching adaptive immunity, DCs are poised to play a critical role in cancer recognition and rejection. As such, DCs represent a solution for the expansion and infiltration of T cells with tumor-rejecting properties. Indeed, clinical responses to checkpoint blockade, such as anti-PD-1, are l...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Martinek J, Wu TC, Cadena D, Banchereau J, Palucka K Tags: Int Rev Cell Mol Biol Source Type: research

Type I interferons and dendritic cells in cancer immunotherapy.
Abstract Type I interferons (IFNs) facilitate cancer immunosurveillance, antitumor immunity and antitumor efficacy of conventional cell death-inducing therapies (chemotherapy/radiotherapy) as well as immunotherapy. Moreover, it is clear that dendritic cells (DCs) play a significant role in aiding type I IFN-driven immunity. Owing to these antitumor properties several immunotherapies involving, or inducing, type I IFNs have received considerable clinical attention, e.g., recombinant IFNα2 or agonists targeting pattern recognition receptor (PRR) pathways like Toll-like receptors (TLRs), cGAS-STING or RIG-I/MDA...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Sprooten J, Agostinis P, Garg AD Tags: Int Rev Cell Mol Biol Source Type: research

Liver DCs in health and disease.
Abstract Hepatic dendritic cells represent a unique and multifaceted subset of antigen-presenting leukocytes that orchestrate specified immune responses in the liver. They are constantly exposed to antigens and signals derived not only from the hepatic microenvironment and the systemic circulation but also from the portal vein draining the gut and conveying food antigens as well as microbial compounds. Modulated by these various factors they shape intrahepatic immune responses during acute and chronic liver diseases, hepatocellular carcinoma and allograft tolerance as well as systemic responses to gut-derived comp...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Wirtz TH, Brandt EF, Berres ML Tags: Int Rev Cell Mol Biol Source Type: research

Antigen processing and presentation.
Abstract Dendritic cells are at the center of immune responses. They are defined by their ability to sense the environment, take up and process antigen, migrate to secondary lymphoid organs, where they present antigens to the adaptive immune system. In particular, they present lipids and proteins from pathogens, which they encountered in peripheral tissues, to T cells in order to induce a specific effector immune response. These complex antigens need to be broken down into peptides of a certain length in association with Major Histocompatibility Complex (MHC) molecules. Presentation of MHC/antigen complexes alongs...
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Kotsias F, Cebrian I, Alloatti A Tags: Int Rev Cell Mol Biol Source Type: research

Preface-Dendritic cells: Master regulators of innate and adaptive immunity.
PMID: 31810557 [PubMed - in process] (Source: International Review of Cell and Molecular Biology)
Source: International Review of Cell and Molecular Biology - December 9, 2019 Category: Cytology Authors: Lhuillier C, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

Origin and development of classical dendritic cells.
Abstract Classical dendritic cells (cDCs) are mononuclear phagocytes of hematopoietic origin specialized in the induction and regulation of adaptive immunity. Initially defined by their unique T cell activation potential, it became quickly apparent that cDCs would be difficult to distinguish from other phagocyte lineages, by solely relying on marker-based approaches. Today, cDCs definition increasingly embed their unique ontogenetic features. A growing consensus defines cDCs on multiple criteria including: (1) dependency on the fms-like tyrosine kinase 3 ligand hematopoietic growth factor, (2) development from the...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Guermonprez P, Gerber-Ferder Y, Vaivode K, Bourdely P, Helft J Tags: Int Rev Cell Mol Biol Source Type: research

The impact of endoplasmic reticulum stress responses in dendritic cell immunobiology.
Abstract Dendritic cells (DCs) are critical for bridging innate and adaptive immunity. They do so by presenting antigens to T cells, and by expressing diverse molecules that further promote T cell activation, differentiation and memory formation. During this process, intracellular and extracellular factors can perturb the protein-folding capacity of endoplasmic reticulum (ER) and induce a cellular state of "ER stress," which is controlled and resolved by the unfolded protein response (UPR). Interestingly, various studies have shown that DCs can activate UPR-related pathways even in the absence of global ...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Salvagno C, Cubillos-Ruiz JR Tags: Int Rev Cell Mol Biol Source Type: research

The versatile plasmacytoid dendritic cell: Function, heterogeneity, and plasticity.
Abstract Since their identification as the natural interferon-producing cell two decades ago, plasmacytoid dendritic cells (pDCs) have been attributed diverse functions in the immune response. Their most well characterized function is innate, i.e., their rapid and robust production of type-I interferon (IFN-I) in response to viruses. However, pDCs have also been implicated in antigen presentation, activation of adaptive immune responses and immunoregulation. The mechanisms by which pDCs enact these diverse functions are poorly understood. One central debate is whether these functions are carried out by different p...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Leylek R, Idoyaga J Tags: Int Rev Cell Mol Biol Source Type: research

Dendritic cell extracellular vesicles.
Abstract In addition to direct cell-to-cell contact, dendritic cells (DCs) can regulate the onset of adaptive immunity through the secretion of nano-sized membrane structures, called extracellular vesicles (EVs). This novel mode of communication between cells has added a new layer of complexity to the regulation of immune responses. DCs secrete into their environment different types of EVs containing immunomodulatory molecules that have distinct structural and biochemical properties depending on their intracellular site of origin. Exosomes are generated inside multivesicular bodies and are secreted when these comp...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Kowal J, Tkach M Tags: Int Rev Cell Mol Biol Source Type: research

Ex vivo dendritic cell generation-A critical comparison of current approaches.
Abstract Dendritic cells (DCs) are professional antigen-presenting cells, required for the initiation of naïve and memory T cell responses and regulation of adaptive immunity. The discovery of DCs in 1973, which culminated in the Nobel Prize in Physiology or Medicine in 2011 for Ralph Steinman and colleagues, initially focused on the identification of adherent mononuclear cell fractions with uniquely stellate dendritic morphology, followed by key discoveries of their critical immunologic role in initiating and maintaining antigen-specific immunity and tolerance. The medical promise of marshaling these key cap...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Han P, Hanlon D, Sobolev O, Chaudhury R, Edelson RL Tags: Int Rev Cell Mol Biol Source Type: research

Transcriptional control of dendritic cell development and functions.
Abstract Dendritic cells (DCs) are major regulators of adaptive immunity, as they are not only capable to induce efficient immune responses, but are also crucial to maintain peripheral tolerance and thereby inhibit autoimmune reactions. DCs bridge the innate and the adaptive immune system by presenting peptides of self and foreign antigens as peptide MHC complexes to T cells. These properties render DCs as interesting target cells for immunomodulatory therapies in cancer, but also autoimmune diseases. Several subsets of DCs with special properties and functions have been described. Recent achievements in understan...
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Amon L, Lehmann CHK, Baranska A, Schoen J, Heger L, Dudziak D Tags: Int Rev Cell Mol Biol Source Type: research

Preface: Dendritic cells: Master regulators of innate and adaptive immunity.
PMID: 31759435 [PubMed - in process] (Source: International Review of Cell and Molecular Biology)
Source: International Review of Cell and Molecular Biology - November 26, 2019 Category: Cytology Authors: Lhuillier C, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

Drugging cancer metabolism: Expectations vs. reality.
Abstract As compared to their normal counterparts, neoplastic cells exhibit a variety of metabolic changes that reflect not only genetic and epigenetic defects underlying malignant transformation, but also the nutritional and immunobiological conditions of the tumor microenvironment. Such alterations, including the so-called Warburg effect (an increase in glucose uptake largely feeding anabolic and antioxidant metabolism), have attracted considerable attention as potential targets for the development of novel anticancer therapeutics. However, very few drugs specifically conceived to target bioenergetic cancer meta...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Montrose DC, Galluzzi L Tags: Int Rev Cell Mol Biol Source Type: research

Diet, lipids and colon cancer.
Abstract Dietary fat is digested and absorbed in the small intestine and can then be utilized as an energy source and/or as a reservoir for other bioactive lipid species. Excessive dietary fat has been implicated in the induction and/or aggravation of several diseases, including colorectal cancer (CRC). Diets with high fat content have been shown to exacerbate CRC through regulation of intestinal inflammation and proliferation, as well as alteration of bile acid pools, microbiota, and bioactive lipid species. This chapter will investigate the effects of dietary fat on CRC development and pathobiology, and possible...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Choi S, Snider AJ Tags: Int Rev Cell Mol Biol Source Type: research

Autophagy and cancer cell metabolism.
Abstract Autophagy is an ancient catabolic process used by cells to clear excess or dysfunctional organelles and large subcellular structures and thus performs an important housekeeping role for the cell. Autophagy is acutely sensitive to nutrient availability and is upregulated at a transcriptional and posttranslational level in response to nutrient deprivation. This serves to promote turnover of cellular content and recycling of nutrients for continued growth and survival. While important for most normal tissues, tumor cells appear to be particularly dependent on autophagy for survival under ischemic or therapeu...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Anderson CM, Macleod KF Tags: Int Rev Cell Mol Biol Source Type: research

Application of metabolomics technologies toward cancer prognosis and therapy.
Abstract Altered metabolism is one of the defining features of cancer. Since the discovery of the Warburg effect in 1924, research into the metabolic aspects of cancer has been reinvigorated over the past decade. Metabolomics is an invaluable tool for gaining insights into numerous biochemical processes including those related to cancer metabolism and metabolic aspects of other diseases. The combination of untargeted and targeted metabolomics approaches has greatly facilitated the discovery of many cancer biomarkers with prognostic potential. Using mass spectrometry-based stable isotope-resolved metabolomics (SIRM...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Hoang G, Udupa S, Le A Tags: Int Rev Cell Mol Biol Source Type: research

A strategy for poisoning cancer cell metabolism: Inhibition of oxidative phosphorylation coupled to anaplerotic saturation.
Abstract The combination of inhibitor of oxidative phosphorylation (OXPHOS) with dimethyl-α-ketoglutarate, a cell-permeable precursor of α-ketoglutarate, is highly efficient in killing human cancer cells in vitro or in vivo, in xenotransplanted mice. This effect involves excessive anaplerosis, as demonstrated by the fact that inhibition of isocitrate dehydrogenase-1, IDH1, reduced the efficacy of cancer cell killing by the combination treatment. However, the signal transduction pathway leading to cell death turned out to be complex because it involved numerous atypical cell death effectors (such as AIF...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Sica V, Bravo-San Pedro JM, Kroemer G Tags: Int Rev Cell Mol Biol Source Type: research

Sulfur metabolism and its contribution to malignancy.
Abstract Metabolic dysregulation is an appreciated hallmark of cancer and a target for therapeutic intervention. Cellular metabolism involves a series of oxidation/reduction (redox) reactions that yield the energy and biomass required for tumor growth. Cells require diverse molecular species with constituent sulfur atoms to facilitate these processes. For humans, this sulfur is derived from the dietary consumption of the proteinogenic amino acids cysteine and methionine, as only lower organisms (e.g., bacteria, fungi, and plants) can synthesize them de novo. In addition to providing the sulfur required to sustain ...
Source: International Review of Cell and Molecular Biology - August 30, 2019 Category: Cytology Authors: Ward NP, DeNicola GM Tags: Int Rev Cell Mol Biol Source Type: research

Molecular platforms for targeted drug delivery.
Abstract The targeted delivery of bioactive molecules to the appropriate site of action, one of the critical focuses of pharmaceutical research, improves therapeutic outcomes and increases safety at the same time; a concept envisaged by Ehrlich over 100 years ago when he described the "magic bullet" model. In the following decades, a considerable amount of research effort combined with enormous investment has carried selective drug targeting into clinical practice via the advent of monoclonal antibodies (mAbs) and antibody-drug conjugates derivatives. Additionally, a deeper understanding of physiopatholo...
Source: International Review of Cell and Molecular Biology - May 29, 2019 Category: Cytology Authors: Maso K, Grigoletto A, Vicent MJ, Pasut G Tags: Int Rev Cell Mol Biol Source Type: research