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Cell Metabolism Dec 2020Acute or chronic cellular stress resulting from aberrant metabolic and biochemical processes may trigger a pervasive non-apoptotic form of cell death, generally known as... (Review)
Review
Acute or chronic cellular stress resulting from aberrant metabolic and biochemical processes may trigger a pervasive non-apoptotic form of cell death, generally known as ferroptosis. Ferroptosis is unique among the different cell death modalities, as it has been mostly linked to pathophysiological conditions and because several metabolic pathways, such as (seleno)thiol metabolism, fatty acid metabolism, iron handling, mevalonate pathway, and mitochondrial respiration, directly impinge on the cells' sensitivity toward lipid peroxidation and ferroptosis. Additionally, key cellular redox systems, such as selenium-dependent glutathione peroxidase 4 and the NAD(P)H/ferroptosis suppressor protein-1/ubiquinone axis, are at play that constantly surveil and neutralize oxidative damage to cellular membranes. Since this form of cell death emerges to be the root cause of a number of diseases and since it offers various pharmacologically tractable nodes for therapeutic intervention, there has been overwhelming interest in the last few years aiming for a better molecular understanding of the ferroptotic death process.
Topics: Animals; Ferroptosis; Humans; Iron; Lipid Metabolism; Lipid Peroxidation; Mitochondria
PubMed: 33217331
DOI: 10.1016/j.cmet.2020.10.011 -
Cell Apr 2023The uptake and metabolism of nutrients support fundamental cellular process from bioenergetics to biomass production and cell fate regulation. While many studies of cell... (Review)
Review
The uptake and metabolism of nutrients support fundamental cellular process from bioenergetics to biomass production and cell fate regulation. While many studies of cell metabolism focus on cancer cells, the principles of metabolism elucidated in cancer cells apply to a wide range of mammalian cells. The goal of this review is to discuss how the field of cancer metabolism provides a framework for revealing principles of cell metabolism and for dissecting the metabolic networks that allow cells to meet their specific demands. Understanding context-specific metabolic preferences and liabilities will unlock new approaches to target cancer cells to improve patient care.
Topics: Animals; Humans; Cell Physiological Phenomena; Energy Metabolism; Mammals; Metabolic Networks and Pathways; Neoplasms; Cells
PubMed: 36858045
DOI: 10.1016/j.cell.2023.01.038 -
Essays in Biochemistry Oct 2020Metabolism consists of a series of reactions that occur within cells of living organisms to sustain life. The process of metabolism involves many interconnected cellular... (Review)
Review
Metabolism consists of a series of reactions that occur within cells of living organisms to sustain life. The process of metabolism involves many interconnected cellular pathways to ultimately provide cells with the energy required to carry out their function. The importance and the evolutionary advantage of these pathways can be seen as many remain unchanged by animals, plants, fungi, and bacteria. In eukaryotes, the metabolic pathways occur within the cytosol and mitochondria of cells with the utilisation of glucose or fatty acids providing the majority of cellular energy in animals. Metabolism is organised into distinct metabolic pathways to either maximise the capture of energy or minimise its use. Metabolism can be split into a series of chemical reactions that comprise both the synthesis and degradation of complex macromolecules known as anabolism or catabolism, respectively. The basic principles of energy consumption and production are discussed, alongside the biochemical pathways that make up fundamental metabolic processes for life.
Topics: Adenosine Triphosphate; Amino Acids; Animals; Bacteria; Citric Acid Cycle; Energy Metabolism; Fatty Acids; Gluconeogenesis; Glycogen; Glycolysis; Humans; Metabolic Diseases; Metabolic Networks and Pathways; Mitochondria; Neoplasms; Plants
PubMed: 32830223
DOI: 10.1042/EBC20190041 -
Cell Research Mar 2018Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental... (Review)
Review
Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view has been instrumental for the development of powerful imaging tools that are still used in the clinics, it is now clear that mitochondria play a key role in oncogenesis. Besides exerting central bioenergetic functions, mitochondria provide indeed building blocks for tumor anabolism, control redox and calcium homeostasis, participate in transcriptional regulation, and govern cell death. Thus, mitochondria constitute promising targets for the development of novel anticancer agents. However, tumors arise, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system, and many immunological functions rely on intact mitochondrial metabolism. Here, we review the cancer cell-intrinsic and cell-extrinsic mechanisms through which mitochondria influence all steps of oncogenesis, with a focus on the therapeutic potential of targeting mitochondrial metabolism for cancer therapy.
Topics: Animals; Antineoplastic Agents; Calcium; Carcinogenesis; Cell Transformation, Neoplastic; Glycolysis; Humans; Mitochondria; Molecular Targeted Therapy; Neoplasms; Oxidation-Reduction
PubMed: 29219147
DOI: 10.1038/cr.2017.155 -
Seminars in Immunopathology Sep 2019Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading... (Review)
Review
Osteoclasts are bone-resorbing cells that play an essential role in the remodeling of the bone. Defects in osteoclasts thus result in unbalanced bone remodeling, leading to numerous pathological conditions such as osteoporosis, bone metastasis, and inflammatory bone erosion. Metabolism is any process a cell utilizes to meet its energetic demand for biological functions. Along with signaling pathways and osteoclast-specific gene expression programs, osteoclast differentiation activates metabolic programs. The energy generated from metabolic reprogramming in osteoclasts not only supports the phenotypic changes from mononuclear precursor cells to multinuclear osteoclasts, but also facilitates bone resorption, a major function of terminally differentiated, mature osteoclasts. While oxidative phosphorylation is studied as a major metabolic pathway that fulfills the energy demands of osteoclasts, all metabolic pathways are closely interconnected. Therefore, it remains important to understand the various aspects of osteoclast metabolism, including the roles and effects of glycolysis, glutaminolysis, fatty acid synthesis, and fatty acid oxidation. Targeting the pathways associated with metabolic reprogramming has shown beneficial effects on pathological conditions. As a result, it is clear that a deeper understanding of metabolic regulation in osteoclasts will offer broader translational potential for the treatment of human bone disorders.
Topics: Animals; Bone Remodeling; Bone Resorption; Bone and Bones; Cellular Reprogramming; Energy Metabolism; Glycolysis; Humans; Lipid Metabolism; Mitochondria; Organelle Biogenesis; Osteoclasts; Oxidative Phosphorylation; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 31552471
DOI: 10.1007/s00281-019-00757-0 -
Immunological Reviews Aug 2023Dendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity.... (Review)
Review
Dendritic cells (DCs) are innate immune cells that detect and process environmental signals and communicate them with T cells to bridge innate and adaptive immunity. Immune signals and microenvironmental cues shape the function of DC subsets in different contexts, which is associated with reprogramming of cellular metabolic pathways. In addition to integrating these extracellular cues to meet bioenergetic and biosynthetic demands, cellular metabolism interplays with immune signaling to shape DC-dependent immune responses. Emerging evidence indicates that lipid metabolism serves as a key regulator of DC responses. Here, we summarize the roles of fatty acid and cholesterol metabolism, as well as selective metabolites, in orchestrating the functions of DCs. Specifically, we highlight how different lipid metabolic programs, including de novo fatty acid synthesis, fatty acid β oxidation, lipid storage, and cholesterol efflux, influence DC function in different contexts. Further, we discuss how dysregulation of lipid metabolism shapes DC intracellular signaling and contributes to the impaired DC function in the tumor microenvironment. Finally, we conclude with a discussion on key future directions for the regulation of DC biology by lipid metabolism. Insights into the connections between lipid metabolism and DC functional specialization may facilitate the development of new therapeutic strategies for human diseases.
Topics: Humans; Lipid Metabolism; Dendritic Cells; Fatty Acids; Cholesterol; Biology
PubMed: 37172120
DOI: 10.1111/imr.13215 -
Journal of Hematology & Oncology Jan 2024The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements.... (Review)
Review
The liver is essential for metabolic homeostasis. The onset of liver cancer is often accompanied by dysregulated liver function, leading to metabolic rearrangements. Overwhelming evidence has illustrated that dysregulated cellular metabolism can, in turn, promote anabolic growth and tumor propagation in a hostile microenvironment. In addition to supporting continuous tumor growth and survival, disrupted metabolic process also creates obstacles for the anticancer immune response and restrains durable clinical remission following immunotherapy. In this review, we elucidate the metabolic communication between liver cancer cells and their surrounding immune cells and discuss how metabolic reprogramming of liver cancer impacts the immune microenvironment and the efficacy of anticancer immunotherapy. We also describe the crucial role of the gut-liver axis in remodeling the metabolic crosstalk of immune surveillance and escape, highlighting novel therapeutic opportunities.
Topics: Humans; Metabolic Reprogramming; Tumor Microenvironment; Neoplasms; Liver Neoplasms; Energy Metabolism; Glycolysis; Immunotherapy
PubMed: 38297372
DOI: 10.1186/s13045-024-01527-8 -
Theranostics 2021Cancer cells are well-known for adapting their metabolism to maintain high proliferation rates and survive in unfavorable environments with low oxygen and nutritional... (Review)
Review
Cancer cells are well-known for adapting their metabolism to maintain high proliferation rates and survive in unfavorable environments with low oxygen and nutritional deficiency. Metabolic reprogramming most commonly arises from the tumor microenvironment (TME). The events of metabolic pathways include the Warburg effect, shift in Krebs cycle metabolites, and increase rate of oxidative phosphorylation that provides the energy for the development and invasion of cancer cells. The TME and shift in tumor metabolism shows a close relationship through bidirectional signaling pathways between the stromal and tumor cells. Cancer-associated fibroblasts (CAFs) are the main type of stromal cells in the TME and consist of a heterogeneous and plastic population that play key roles in tumor growth and metastatic capacity. Emerging evidence suggests that CAFs act as major regulators in shaping tumor metabolism especially through the dysregulation of several metabolic pathways, including glucose, amino acid, and lipid metabolism. The arrangement of these metabolic switches is believed to shape distinct CAF behavior and change tumor cell behavior by the CAFs. The crosstalk between cancer cells and CAFs is associated with cell metabolic reprogramming that contributes to cancer cell growth, progression, and evasion from cancer therapies. But the mechanism and process of this interaction remain unclear. This review aimed to highlight the metabolic couplings between tumor cells and CAFs. We reviewed the recent literature supporting an important role of CAFs in the regulation of cancer cell metabolism, and the relevant pathways, which may serve as targets for therapeutic interventions.
Topics: Animals; Cancer-Associated Fibroblasts; Cellular Reprogramming; Drug Delivery Systems; Humans; Neoplasms; Oxidative Phosphorylation; Signal Transduction; Stromal Cells; Tumor Microenvironment
PubMed: 34373744
DOI: 10.7150/thno.62378 -
Mitochondrion May 2014The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical,... (Review)
Review
The cell danger response (CDR) is the evolutionarily conserved metabolic response that protects cells and hosts from harm. It is triggered by encounters with chemical, physical, or biological threats that exceed the cellular capacity for homeostasis. The resulting metabolic mismatch between available resources and functional capacity produces a cascade of changes in cellular electron flow, oxygen consumption, redox, membrane fluidity, lipid dynamics, bioenergetics, carbon and sulfur resource allocation, protein folding and aggregation, vitamin availability, metal homeostasis, indole, pterin, 1-carbon and polyamine metabolism, and polymer formation. The first wave of danger signals consists of the release of metabolic intermediates like ATP and ADP, Krebs cycle intermediates, oxygen, and reactive oxygen species (ROS), and is sustained by purinergic signaling. After the danger has been eliminated or neutralized, a choreographed sequence of anti-inflammatory and regenerative pathways is activated to reverse the CDR and to heal. When the CDR persists abnormally, whole body metabolism and the gut microbiome are disturbed, the collective performance of multiple organ systems is impaired, behavior is changed, and chronic disease results. Metabolic memory of past stress encounters is stored in the form of altered mitochondrial and cellular macromolecule content, resulting in an increase in functional reserve capacity through a process known as mitocellular hormesis. The systemic form of the CDR, and its magnified form, the purinergic life-threat response (PLTR), are under direct control by ancient pathways in the brain that are ultimately coordinated by centers in the brainstem. Chemosensory integration of whole body metabolism occurs in the brainstem and is a prerequisite for normal brain, motor, vestibular, sensory, social, and speech development. An understanding of the CDR permits us to reframe old concepts of pathogenesis for a broad array of chronic, developmental, autoimmune, and degenerative disorders. These disorders include autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), asthma, atopy, gluten and many other food and chemical sensitivity syndromes, emphysema, Tourette's syndrome, bipolar disorder, schizophrenia, post-traumatic stress disorder (PTSD), chronic traumatic encephalopathy (CTE), traumatic brain injury (TBI), epilepsy, suicidal ideation, organ transplant biology, diabetes, kidney, liver, and heart disease, cancer, Alzheimer and Parkinson disease, and autoimmune disorders like lupus, rheumatoid arthritis, multiple sclerosis, and primary sclerosing cholangitis.
Topics: Brain; Disease; Energy Metabolism; Health; Homeostasis; Humans; Metabolic Networks and Pathways; Mitochondria; Stress, Physiological
PubMed: 23981537
DOI: 10.1016/j.mito.2013.08.006 -
Annual Review of Biochemistry 2012Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores... (Review)
Review
Among organelles, lipid droplets (LDs) uniquely constitute a hydrophobic phase in the aqueous environment of the cytosol. Their hydrophobic core of neutral lipids stores metabolic energy and membrane components, making LDs hubs for lipid metabolism. In addition, LDs are implicated in a number of other cellular functions, ranging from protein storage and degradation to viral replication. These processes are functionally linked to many physiological and pathological conditions, including obesity and related metabolic diseases. Despite their important functions and nearly ubiquitous presence in cells, many aspects of LD biology are unknown. In the past few years, the pace of LD investigation has increased, providing new insights. Here, we review the current knowledge of LD cell biology and its translation to physiology.
Topics: Animals; Cells; Humans; Lipid Metabolism; Lipids; Lipolysis; Metabolic Diseases; Obesity; Organelles
PubMed: 22524315
DOI: 10.1146/annurev-biochem-061009-102430