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Annals of Botany Nov 2023This review summarizes recent advances in our understanding of Crassulacean Acid Metabolism (CAM) by integrating evolutionary, ecological, physiological, metabolic and... (Review)
Review
BACKGROUND AND SCOPE
This review summarizes recent advances in our understanding of Crassulacean Acid Metabolism (CAM) by integrating evolutionary, ecological, physiological, metabolic and molecular perspectives. A number of key control loops which moderate the expression of CAM phases, and their metabolic and molecular control, are explored. These include nocturnal stomatal opening, activation of phosphoenolpyruvate carboxylase by a specific protein kinase, interactions with circadian clock control, as well as daytime decarboxylation and activation of Rubisco. The vacuolar storage and release of malic acid and the interplay between the supply and demand for carbohydrate reserves are also key metabolic control points.
FUTURE OPPORTUNITIES
We identify open questions and opportunities, with experimentation informed by top-down molecular modelling approaches allied with bottom-up mechanistic modelling systems. For example, mining transcriptomic datasets using high-speed systems approaches will help to identify targets for future genetic manipulation experiments to define the regulation of CAM (whether circadian or metabolic control). We emphasize that inferences arising from computational approaches or advanced nuclear sequencing techniques can identify potential genes and transcription factors as regulatory targets. However, these outputs then require systematic evaluation, using genetic manipulation in key model organisms over a developmental progression, combining gene silencing and metabolic flux analysis and modelling to define functionality across the CAM day-night cycle. From an evolutionary perspective, the origins and function of CAM succulents and responses to water deficits are set against the mesophyll and hydraulic limitations imposed by cell and tissue succulence in contrasting morphological lineages. We highlight the interplay between traits across shoots (3D vein density, mesophyll conductance and cell shrinkage) and roots (xylem embolism and segmentation). Thus, molecular, biophysical and biochemical processes help to curtail water losses and exploit rapid rehydration during restorative rain events. In the face of a changing climate, we hope such approaches will stimulate opportunities for future research.
Topics: Crassulacean Acid Metabolism; Photosynthesis; Phosphoenolpyruvate Carboxylase; Biological Evolution; Water
PubMed: 37742290
DOI: 10.1093/aob/mcad142 -
International Journal of Biological... 2023Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and... (Review)
Review
Adipocytes are adipose tissues that supply energy to the body through lipids. The two main types of adipocytes comprise white adipocytes (WAT) that store energy, and brown adipocytes (BAT), which generate heat by burning stored fat (thermogenesis). Emerging evidence indicates that dysregulated adipocyte senescence may disrupt metabolic homeostasis, leading to various diseases and aging. Adipocytes undergo senescence via irreversible cell-cycle arrest in response to DNA damage, oxidative stress, telomere dysfunction, or adipocyte over-expansion upon chronic lipid accumulation. The amount of detectable BAT decreases with age. Activation of cell cycle regulators and dysregulation of adipogenesis-regulating factors may constitute a molecular mechanism that accelerates adipocyte senescence. To better understand the regulation of adipocyte senescence, the effects of post-translational modifications (PTMs), is essential for clarifying the activity and stability of these proteins. PTMs are covalent enzymatic protein modifications introduced following protein biosynthesis, such as phosphorylation, acetylation, ubiquitination, or glycosylation. Determining the contribution of PTMs to adipocyte senescence may identify new therapeutic targets for the regulation of adipocyte senescence. In this review, we discuss a conceptual case in which PTMs regulate adipocyte senescence and explain the mechanisms underlying protein regulation, which may lead to the development of effective strategies to combat metabolic diseases.
Topics: Adipose Tissue, Brown; Adipocytes, Brown; Adipogenesis; Protein Processing, Post-Translational; Cell Cycle Checkpoints
PubMed: 37928271
DOI: 10.7150/ijbs.86404 -
Cell Death & Disease Jun 2024Diabetic kidney disease, known as a glomerular disease, arises from a metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play a key role... (Review)
Review
Diabetic kidney disease, known as a glomerular disease, arises from a metabolic disorder impairing renal cell function. Mitochondria, crucial organelles, play a key role in substance metabolism via oxidative phosphorylation to generate ATP. Cells undergo metabolic reprogramming as a compensatory mechanism to fulfill energy needs for survival and growth, attracting scholarly attention in recent years. Studies indicate that mitochondrial metabolic reprogramming significantly influences the pathophysiological progression of DKD. Alterations in kidney metabolism lead to abnormal expression of signaling molecules and activation of pathways, inducing oxidative stress-related cellular damage, inflammatory responses, apoptosis, and autophagy irregularities, culminating in renal fibrosis and insufficiency. This review delves into the impact of mitochondrial metabolic reprogramming on DKD pathogenesis, emphasizing the regulation of metabolic regulators and downstream signaling pathways. Therapeutic interventions targeting renal metabolic reprogramming can potentially delay DKD progression. The findings underscore the importance of focusing on metabolic reprogramming to develop safer and more effective therapeutic approaches.
Topics: Humans; Diabetic Nephropathies; Mitochondria; Animals; Signal Transduction; Oxidative Stress; Kidney; Metabolic Reprogramming
PubMed: 38910210
DOI: 10.1038/s41419-024-06833-0 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... Nov 2023A ketogenic diet limits energy supply from glucose and stimulates lipolysis, lipid oxidation, and ketogenesis, resulting in elevated levels of ketone bodies in the... (Review)
Review
A ketogenic diet limits energy supply from glucose and stimulates lipolysis, lipid oxidation, and ketogenesis, resulting in elevated levels of ketone bodies in the bloodstream. Ketone bodies are synthesized in the mitochondrial matrix of liver cells and β-hydroxybutyric acid (BHB) is the most abundant type of ketone body. Herein, we reviewed published findings on the metabolism of ketone bodies and the role of BHB in renal diseases. Through blood circulation, ketone bodies reach metabolically active tissues and provides an alternative source of energy. BHB, being a signaling molecule, mediates various types of cellular signal transduction and participates in the development and progression of many diseases. BHB also has protective and therapeutic effects on a variety of renal diseases. BHB improves the prognosis of renal diseases, such as diabetic kidney disease, chronic kidney disease, acute kidney injury, and polycystic kidney disease, through its antioxidant, anti-inflammatory, and stress response mechanisms. Previous studies have focused on the role of ketone bodies in regulating inflammation and oxidative stress in immune cells. Investigations into the effect of elevated levels of ketone bodies on the metabolism of renal podocytes and tubular cells remain inconclusive. Further research is needed to investigate the effect of BHB on podocyte damage and podocyte senescence in renal diseases.
Topics: Humans; Ketone Bodies; 3-Hydroxybutyric Acid; Oxidative Stress; Antioxidants; Kidney; Kidney Diseases
PubMed: 38162055
DOI: 10.12182/20231160202 -
Cell Death & Disease Jul 2023Accumulating evidence indicates that metabolic responses are deeply integrated into signal transduction, which provides novel opportunities for the metabolic control of...
Accumulating evidence indicates that metabolic responses are deeply integrated into signal transduction, which provides novel opportunities for the metabolic control of various disorders. Recent studies suggest that itaconate, a highly concerned bioactive metabolite catalyzed by immune responsive gene 1 (IRG1), is profoundly involved in the regulation of apoptosis, but the underlying mechanisms have not been fully understood. In the present study, the molecular mechanisms responsible for the apoptosis-modulatory activities of IRG1/itaconate have been investigated in mice with lipopolysaccharide (LPS)/D-galactosamine (D-Gal)-induced apoptotic liver injury. The results indicated that LPS/D-Gal exposure upregulated the level of IRG1 and itaconate. Deletion of IRG1 resulted in exacerbated hepatocytes apoptosis and liver injury. The phospho-antibody microarray analysis and immunoblot analysis indicated that IRG1 deletion enhanced the activation of AMP-activated protein kinase (AMPK)/c-jun-N-terminal kinase (JNK) pathway in LPS/D-Gal exposed mice. Mechanistically, IRG1 deficiency impaired the anti-oxidative nuclear factor erythroid-2 related factor 2 (Nrf2) signaling and then enhanced the activation of the redox-sensitive AMPK/JNK pathway that promotes hepatocytes apoptosis. Importantly, post-insult supplementation with 4-octyl itaconate (4-OI), a cell-permeable derivate of itaconate, resulted in beneficial outcomes in fulminant liver injury. Therefore, IRG1/itaconate might function as a negative regulator that controls AMPK-induced hepatocyte apoptosis in LPS/D-Gal-induced fulminant liver injury.
Topics: Animals; Mice; MAP Kinase Signaling System; AMP-Activated Protein Kinases; Apoptosis Regulatory Proteins; Lipopolysaccharides; Liver; NF-E2-Related Factor 2
PubMed: 37524706
DOI: 10.1038/s41419-023-06001-w -
Epigenetics & Chromatin Nov 2023Chromatin plays a central role in the conversion of energy in cells: alteration of chromatin structure to make DNA accessible consumes energy, and compaction of... (Review)
Review
Chromatin plays a central role in the conversion of energy in cells: alteration of chromatin structure to make DNA accessible consumes energy, and compaction of chromatin preserves energy. Alteration of chromatin structure uses energy sources derived from carbon metabolism such as ATP and acetyl-CoA; conversely, chromatin compaction and epigenetic modification feedback to metabolism and energy homeostasis by controlling gene expression and storing metabolites. Coordination of these dual chromatin events must be flexibly modulated in response to environmental changes such as during development and exposure to stress. Aging also alters chromatin structure and the coordination of metabolism, chromatin dynamics, and other cell processes. Noncoding RNAs and other RNA species that associate directly with chromatin or with chromatin modifiers contribute to spatiotemporal control of transcription and energy conversion. The time required for generating the large amounts of RNAs and chromatin modifiers observed in super-enhancers may be critical for regulation of transcription and may be impacted by aging. Here, taking into account these factors, we review alterations of chromatin that are fundamental to cell responses to metabolic changes due to stress and aging to maintain redox and energy homeostasis. We discuss the relationship between spatiotemporal control of energy and chromatin function, as this emerging concept must be considered to understand how cell homeostasis is maintained.
Topics: Chromatin; Oxidation-Reduction; Epigenesis, Genetic; Homeostasis
PubMed: 38017471
DOI: 10.1186/s13072-023-00520-8 -
Frontiers in Immunology 2023A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact... (Review)
Review
A significant factor in the antitumor immune response is the increased metabolic reprogramming of immunological and malignant cells. Increasing data points to the fact that cancer metabolism affects not just cancer signaling, which is essential for maintaining carcinogenesis and survival, but also the expression of immune cells and immune-related factors such as lactate, PGE2, arginine, IDO, which regulate the antitumor immune signaling mechanism. In reality, this energetic interaction between the immune system and the tumor results in metabolic competition in the tumor ecosystem, limiting the amount of nutrients available and causing microenvironmental acidosis, which impairs the ability of immune cells to operate. More intriguingly, different types of immune cells use metabolic reprogramming to keep the body and self in a state of homeostasis. The process of immune cell proliferation, differentiation, and performance of effector functions, which is crucial to the immune response, are currently being linked to metabolic reprogramming. Here, we cover the regulation of the antitumor immune response by metabolic reprogramming in cancer cells and immune cells as well as potential strategies for metabolic pathway targeting in the context of anticancer immunotherapy. We also discuss prospective immunotherapy-metabolic intervention combinations that might be utilized to maximize the effectiveness of current immunotherapy regimes.
Topics: Humans; Metabolic Reprogramming; Ecosystem; Prospective Studies; Carcinogenesis; Neoplasms; Immunosuppression Therapy; Hypoxia
PubMed: 38292487
DOI: 10.3389/fimmu.2023.1325360 -
Nature Communications Oct 2023Current approaches in myocardial infarction treatment are limited by low cellular oxidative stress resistance, reducing the long-term survival of therapeutic cells. Here...
Current approaches in myocardial infarction treatment are limited by low cellular oxidative stress resistance, reducing the long-term survival of therapeutic cells. Here we develop a liquid-crystal substrate with unique surface properties and mechanical responsiveness to produce size-controllable cardiospheres that undergo pyroptosis to improve cellular bioactivities and resistance to oxidative stress. We perform RNA sequencing and study cell metabolism to reveal increased metabolic levels and improved mitochondrial function in the preconditioned cardiospheres. We test therapeutic outcomes in a rat model of myocardial infarction to show that cardiospheres improve long-term cardiac function, promote angiogenesis and reduce cardiac remodeling during the 3-month observation. Overall, this study presents a promising and effective system for preparing a large quantity of functional cardiospheres, showcasing potential for clinical application.
Topics: Rats; Animals; Myocytes, Cardiac; Pyroptosis; Myocardial Infarction; Spheroids, Cellular; Oxidative Stress
PubMed: 37783697
DOI: 10.1038/s41467-023-41700-0 -
Cells Oct 2023The complexities of translational strategies make this stage of implementing genetic information one of the most challenging to comprehend and, simultaneously, perhaps... (Review)
Review
The complexities of translational strategies make this stage of implementing genetic information one of the most challenging to comprehend and, simultaneously, perhaps the most engaging. It is evident that this diverse range of strategies results not only from a long evolutionary history, but is also of paramount importance for refining gene expression and metabolic modulation. This notion is particularly accurate for organisms that predominantly exhibit biochemical and physiological reactions with a lack of behavioural ones. Plants are a group of organisms that exhibit such features. Addressing unfavourable environmental conditions plays a pivotal role in plant physiology. This is particularly evident with the changing conditions of global warming and the irrevocable loss or depletion of natural ecosystems. In conceptual terms, the plant response to abiotic stress comprises a set of elaborate and intricate strategies. This is influenced by a range of abiotic factors that cause stressful conditions, and molecular genetic mechanisms that fine-tune metabolic pathways allowing the plant organism to overcome non-standard and non-optimal conditions. This review aims to focus on the current state of the art in the field of translational regulation in plants under abiotic stress conditions. Different regulatory elements and patterns are being assessed chronologically. We deem it important to focus on significant high-performance techniques for studying the genetic information dynamics during the translation phase.
Topics: Ecosystem; Plants; Plant Physiological Phenomena; Metabolic Networks and Pathways; Stress, Physiological
PubMed: 37887289
DOI: 10.3390/cells12202445 -
Science Advances Nov 2023Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity... (Review)
Review
Poor oxygenation (hypoxia) is a common spatially heterogeneous feature of human tumors. Biological responses to tumor hypoxia are orchestrated by the decreased activity of oxygen-dependent enzymes. The affinity of these enzymes for oxygen positions them along a continuum of oxygen sensing that defines their roles in launching reactive and adaptive cellular responses. These responses encompass regulation of all steps in the central dogma, with rapid perturbation of the metabolome and proteome followed by more persistent reprogramming of the transcriptome and epigenome. Core hypoxia response genes and pathways are commonly regulated at multiple inflection points, fine-tuning the dependencies on oxygen concentration and hypoxia duration. Ultimately, shifts in the activity of oxygen-sensing enzymes directly or indirectly endow cells with intrinsic hypoxia tolerance and drive processes that are associated with aggressive phenotypes in cancer including angiogenesis, migration, invasion, immune evasion, epithelial mesenchymal transition, and stemness.
Topics: Humans; Tumor Hypoxia; Neoplasms; Hypoxia; Oxygen; Phenotype
PubMed: 37992163
DOI: 10.1126/sciadv.adj6409