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Lysosomes play a pivotal role in coordinating macromolecule degradation and regulating cell growth and metabolism. Despite substantial progress in identifying lysosomal signaling proteins, understanding the pathways that synchronize lysosome functions with changing cellular demands remains incomplete. This study uncovers a role for TANK-binding kinase 1 (TBK1), well known for its role in innate immunity and organelle quality control, in modulating lysosomal responsiveness to nutrients. Specifically, we identify a pool of TBK1 that is recruited to lysosomes in response to elevated amino acid levels. This lysosomal TBK1 phosphorylates Rab7 on serine 72. This is critical for alleviating Rab7-mediated inhibition of amino acid-dependent mTORC1 activation. Furthermore, a TBK1 mutant (E696K) associated with amyotrophic lateral sclerosis and frontotemporal dementia constitutively accumulates at lysosomes, resulting in elevated Rab7 phosphorylation and increased mTORC1 activation. This data establishes the lysosome as a site of amino acid regulated TBK1 signaling that is crucial for efficient mTORC1 activation. This lysosomal pool of TBK1 has broader implications for lysosome homeostasis, and its dysregulation could contribute to the pathogenesis of ALS-FTD. Synopsis: In addition to their degradative functions, lysosomes play an important role in coordinating cellular responses to changes in nutrient availability. This study reveals that TBK1 is recruited to lysosomes when amino acids are abundant where it phosphorylates Rab7 and thus relieves Rab7-dependent suppression of mTORC1 signaling from lysosomes. TBK1 is recruited to lysosomes when amino acids are abundant. Rab7 (serine 72) is a substrate of TBK1 at lysosomes. Rab7 suppresses mTORC1 activity and this is relieved by TBK1-dependent phosphorylation of Rab7 on serine 72. The ALS-FTD associated E696K TBK1 mutant accumulates at lysosomes resulting in increased Rab7 phosphorylation and mTORC1 activity. TBK1 promotes mTORC1 activation by amino acids at the lysosome surface. [ABSTRACT FROM AUTHOR]

The mechanistic target of rapamycin complex 1 (mTORC1) pathway regulates cell growth and metabolism in response to many environmental cues, including nutrients. Amino acids signal to mTORC1 by modulating the guanine nucleotide loading states of the heterodimeric Rag GTPases, which bind and recruit mTORC1 to the lysosomal surface, its site of activation. The Rag GTPases are tethered to the lysosome by the Ragulator complex and regulated by the GATOR1, GATOR2, and KICSTOR multiprotein complexes that localize to the lysosomal surface through an unknown mechanism(s). Here, we show that mTORC1 is completely insensitive to amino acids in cells lacking the Rag GTPases or the Ragulator component p18. Moreover, not only are the Rag GTPases and Ragulator required for amino acids to regulate mTORC1, they are also essential for the lysosomal recruitment of the GATOR1, GATOR2, and KICSTOR complexes, which stably associate and traffic to the lysosome as the "GATOR" supercomplex. The nucleotide state of RagA/B controls the lysosomal association of GATOR, in a fashion competitively antagonized by the N terminus of the amino acid transporter SLC38A9. Targeting of Ragulator to the surface of mitochondria is sufficient to relocalize the Rags and GATOR to this organelle, but not to enable the nutrient-regulated recruitment of mTORC1 to mitochondria. Thus, our results reveal that the Rag-Ragulator complex is the central organizer of the physical architecture of the mTORC1 nutrient-sensing pathway and underscore that mTORC1 activation requires signal transduction on the lysosomal surface. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a lethal disease with limited effective treatments. A deeper understanding of its molecular mechanisms is crucial to reduce incidence and mortality. Epidemiological evidence suggests a link between diet and disease risk, though dietary recommendations for at‐risk individuals remain debated. Here, we propose that cell‐intrinsic nutrient sensing pathways respond to specific diet‐derived cues to facilitate oncogenic transformation of pancreatic epithelial cells. This review explores how diet influences pancreatic cancer predisposition through nutrient sensing and downstream consequences for (pre‐)cancer cell biology. We also examine experimental evidence connecting specific food intake to pancreatic cancer progression, highlighting nutrient sensing as a promising target for therapeutic development to mitigate disease risk. [ABSTRACT FROM AUTHOR]

The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G‐protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient–receptor interaction causes the release of hormonal stores such as glucagon‐like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet‐derived luminal components and microbial products and nutrient‐sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells. [ABSTRACT FROM AUTHOR]

Gastrointestinal nutrient sensing via taste receptors may contribute to weight loss, metabolic improvements, and a reduced preference for sweet and fatty foods following bariatric surgery. This review aimed to investigate the effect of bariatric surgery on the expression of oral and post-oral gastrointestinal taste receptors and associations between taste receptor alterations and clinical outcomes of bariatric surgery. A systematic review was conducted to capture data from both human and animal studies on changes in the expression of taste receptors in oral or post-oral gastrointestinal tissue following any type of bariatric surgery. Databases searched included Medline, Embase, Emcare, APA PsychInfo, Cochrane Library, and CINAHL. Two human and 21 animal studies were included. Bariatric surgery alters the quantity of many sweet, umami, and fatty acid taste receptors in the gastrointestinal tract. Changes to the expression of sweet and amino acid receptors occur most often in intestinal segments surgically repositioned more proximally, such as the alimentary limb after gastric bypass. Conversely, changes to fatty acid receptors were observed more frequently in the colon than in the small intestine. Significant heterogeneity in the methodology of included studies limited conclusions regarding the direction of change in taste receptor expression induced by bariatric surgeries. Few studies have investigated associations between taste receptor expression and clinical outcomes of bariatric surgery. As such, future studies should look to investigate the relationship between bariatric surgery-induced changes to gut taste receptor expression and function and the impact of surgery on taste preferences, food palatability, and eating behaviour. Registration code in PROSPERO: CRD42022313992 [ABSTRACT FROM AUTHOR]

Heterotrimeric GTP-binding proteins or G-proteins are pivotal players in the intricate signaling cascades of plant cells, operating through their binding to guanine nucleotides. These G-proteins primarily consist of three essential subunits: Gα, Gβ, and Gγ. Among these subunits, Gγ stands out for its remarkable genetic diversity. In the present investigation, six Gγ subunits were identified in the Indian variety T-163 of the pea plant (Pisum sativum). Notably, two of these novel Gγ subunits, named PsGγ1 and PsGγ2, belong to type A, while PsGγ3 falls within the type B category. The remaining three subunits, namely PsGγ4, PsGγ5, and PsGγ6, are classified under type C. An in-depth comparison of the amino acid sequences of these pea Gγ subunits with their counterparts in other plants, including Arabidopsis thaliana and Oryza sativa, has unveiled significant variations. This research explores the impact of different treatments on PsGγ genes (PsGγ1 to PsGγ6) in plants. Noteworthy discoveries include a 4-fold increase in the expression of PsGγ1, PsGγ4, PsGγ5, and PsGγ6 in the presence of nitrogen. PsGγ2 and PsGγ3, however, show no response. Phosphorus induces a 3-fold upregulation in PsGγ2 and PsGγ4, and a 4-fold increase in PsGγ5. Conversely, the absence of phosphorus triggers a 4-fold upregulation in PsGγ4 and PsGγ5. Heat stress leads to a 3-fold upregulation in PsGγ2, PsGγ4, and PsGγ5, while cold stress results in a 3-fold upregulation of PsGγ1 and PsGγ6. Under high salt conditions, PsGγ1, PsGγ3, PsGγ4, and PsGγ6 exhibit a 4-fold upregulation, with PsGγ2 showing a 2-fold increase. PsGγ4 and PsGγ5 display a 4-fold upregulation in response to ABA, while PsGγ2 and PsGγ3 show a 3-fold increase while MeJA induces a 4-fold upregulation in PsGγ5. Notably, this study unveils, for the first time, the significant role of Gγ subunits during endosymbiotic associations with phosphorus-acquiring AMF with AMF triggering a 4-fold upregulation in PsGγ4 and PsGγ6. The presence of multiple Gγ subunits in pea underscores their critical participation in governing plant development, stress responses, nutrient sensing, and interactions with mycorrhizal fungi.

Background: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. Scope of Review: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. Major Conclusions: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

Abstract The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G‐protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient–receptor interaction causes the release of hormonal stores such as glucagon‐like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet‐derived luminal components and microbial products and nutrient‐sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells.

The central nervous system (CNS) relies on myelin for proper functioning. Myelin remodeling is a risk factor for neurometabolic and endocrine malfunction, resulting in cognitive decline and heightened susceptibility to neurological diseases. The plasticity of myelin upon nutrient shifts may lead to dietary and hormonal interventions for preventing and treating neural complications. [ABSTRACT FROM AUTHOR]

Increased anthropogenic emissions of carbon dioxide (CO2) have resulted in ocean acidification (OA) that is intertwined with enhanced ocean stratification. Diatoms are assumed to suffer from a more nutrient-limited condition in the future ocean. This study aimed to explore how OA affects the diatom dynamics under nutrient-poor conditions and the ability of diatoms to perceive nutrients (nitrogen, phosphorus, silicon, and trace metals) and cadmium (Cd) stimuli and assimilate nitrogen when receiving nutrients or Cd supplementation. Our study observed that diatom population grown under OA condition declined faster than those grown under ambient condition. Ocean acidification greatly lower intracellular Ca2+ concentration in diatom cells. Intracellular Ca2+ burst was involved in phosphorus accumulation but not in nitrogen, silicon, essential metals, and cadmium uptake. Our data demonstrate slower NO3– assimilation rates of diatoms grown in acidified seawater. Our study also indicates that diatoms have a poor perception of phosphorus availability under OA condition. [ABSTRACT FROM AUTHOR]

Differentiation and fate decisions are critical for the epithelial cells lining the proximal tubule (PT) of the kidney, but the signals involved remain unknown. Defective cystine mobilization from lysosomes through CTNS (cystinosin, lysosomal cystine transporter), which is mutated in cystinosis, triggers the dedifferentiation and dysfunction of the PT cells, causing kidney disease and severe metabolic complications. Using preclinical models and physiologically relevant cellular systems, along with functional assays and a generative artificial intelligence (AI)-powered engine, we found that cystine storage imparted by CTNS deficiency stimulates Ragulator-RRAG GTPase-dependent recruitment of MTORC1 and its constitutive activation. In turn, this diverts the catabolic trajectories and differentiating states of PT cells toward growth and proliferation, disrupting homeostasis and their specialized functions. Therapeutic MTORC1 inhibition by using low doses of rapamycin corrects lysosome function and differentiation downstream of cystine storage and ameliorates PT dysfunction in preclinical models of cystinosis. These discoveries suggest that cystine may act as a lysosomal fasting signal that tailors MTORC1 signaling to direct fate decisions in the kidney PT epithelium, highlighting novel therapeutic paradigms for cystinosis and other lysosome-related disorders. [ABSTRACT FROM AUTHOR]

Water and soil nutrients are the vital ingredients of crop production, and their efficient uptake is essentially dependent on root development, majorly regulated by auxin. For a water-loving crop like rice, how water availability regulates nutrient acquisition, additionally, how ambient nutrient level modulates water uptake, and the role of auxin therein is not well studied. While investigating the cross-talks among these components, we found water to be essential for auxin re-distribution in roots and shaping the root architecture. We also found that supplementing rice seedlings with moderate concentrations of mineral nutrients facilitated faster water uptake and greater nutrient enrichment in leaves compared to adequate nutrient supplementation. Additionally, moderate nutrient availability favoured greater stomatal density, stomatal conductance, photosynthesis, transpiration rate and water use efficiency when water was not limiting. Further, auxin supplementation enhanced root formation in rice, while affecting their water uptake ability, photosynthesis and transpiration causing differential mineral-specific uptake trends. The present study uncovers the existence of an intricate crosstalk among water, nutrients and auxin signalling the knowledge of which will enable optimizing the growth conditions for speed breeding of rice and harnessing the components of auxin signalling to improve water and nutrient use efficiency of rice., (© 2024 John Wiley & Sons Ltd.)

The human pathogen Pseudomonas aeruginosa , a leading cause of hospital-acquired infections, inhabits and forms sessile antibiotic-resistant communities called biofilms in a wide range of biotic and abiotic environments. In this study, we examined how two global sensory signaling pathways-the RhlR quorum-sensing system and the CbrA/CbrB nutritional adaptation system-intersect to control biofilm development. Previous work has shown that individually these two systems repress biofilm formation. Here, we used biofilm analyses, RNA-seq, and reporter assays to explore the combined effect of information flow through RhlR and CbrA on biofilm development. We find that the Δ rhlR Δ cbrA double mutant exhibits a biofilm morphology and an associated transcriptional response distinct from wildtype and the parent Δ rhlR and Δ cbrA mutants indicating codominance of each signaling pathway. The Δ rhlR Δ cbrA mutant gains suppressor mutations that allow biofilm expansion; these mutations map to the crc gene resulting in loss of function of the carbon catabolite repression protein Crc. Furthermore, the combined absence of RhlR and CbrA leads to a drastic reduction in the abundance of the Crc antagonist small RNA CrcZ. Thus, CrcZ acts as the molecular convergence point for quorum- and nutrient-sensing cues. We find that in the absence of antagonism by CrcZ, Crc promotes the expression of biofilm matrix components-Pel exopolysaccharide, and CupB and CupC fimbriae. Therefore, this study uncovers a regulatory link between nutritional adaption and quorum sensing with potential implications for anti-biofilm targeting strategies.IMPORTANCEBacteria often form multicellular communities encased in an extracytoplasmic matrix called biofilms. Biofilm development is controlled by various environmental stimuli that are decoded and converted into appropriate cellular responses. To understand how information from two distinct stimuli is integrated, we used biofilm formation in the human pathogen Pseudomonas aeruginosa as a model and studied the intersection of two global sensory signaling pathways-quorum sensing and nutritional adaptation. Global transcriptomics on biofilm cells and reporter assays suggest parallel regulation of biofilms by each pathway that converges on the abundance of a small RNA antagonist of the carbon catabolite repression protein, Crc. We find a new role of Crc as it modulates the expression of biofilm matrix components in response to the environment. These results expand our understanding of the genetic regulatory strategies that allow P. aeruginosa to successfully develop biofilm communities., Competing Interests: The authors declare no conflict of interest.

The mechanistic target of rapamycin complex 1 (mTORC1) is indispensable for preserving cellular and organismal homeostasis by balancing the anabolic and catabolic processes in response to various environmental cues, such as nutrients, growth factors, energy status, oxygen levels, and stress. Dysregulation of mTORC1 signaling is associated with the progression of many types of human disorders including cancer, age-related diseases, neurodegenerative disorders, and metabolic diseases. The way mTORC1 senses various upstream signals and converts them into specific downstream responses remains a crucial question with significant impacts for our perception of the related physiological and pathological process. In this review, we discuss the recent molecular and functional insights into the nutrient sensing of the mTORC1 signaling pathway, along with the emerging role of deregulating nutrient-mTORC1 signaling in cancer and age-related disorders., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest A conflicting interest exists when professional judgement concerning a primary interest (such as patient’s welfare or the validity of research) may be influenced by a secondary interest (such as financial gain or personal rivalry). It may arise for the authors when they have financial interest that may influence their interpretation of their results or those of others. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

The hypothalamus plays a crucial role in regulating feeding behavior in fish. In this Review, we aim to summarise current knowledge on specific mechanisms for sensing glucose, fatty acids and amino acids in fish, and to consider how this information is integrated in the hypothalamus to modulate feed intake. In fish, specific neuronal populations in the nucleus lateralis tuberalis (NLTv) of the hypothalamus are equipped with nutrient sensors and hormone receptors, allowing them to respond to changes in metabolite levels and hormonal signals. These neurons produce orexigenic (Npy and Agrp) and anorexigenic (Pomc and Cart) neuropeptides, which stimulate and suppress appetite, respectively. The modulation of feeding behavior involves adjusting the expression of these neuropeptides based on physiological conditions, ultimately influencing feeding through reciprocal inhibition of anorexigenic and orexigenic neurons and signalling to higher-order neurons. The activation of nutrient sensors in fish leads to an enhanced anorexigenic effect, with downregulation of agrp and npy, and upregulation of cart and pomc. Connections between hypothalamic neurons and other populations in various brain regions contribute to the intricate regulation of feeding behaviour in fish. Understanding how feed intake is regulated in fish through these processes is relevant to understanding fish evolution and is also important in the context of aquaculture., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)

Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily. [Display omitted] [ABSTRACT FROM AUTHOR]

Autoimmune diseases exhibit a pronounced yet unexplained prevalence among women. Vestigial-like family member 3 (VGLL3), a female-biased factor that promotes autoimmunity, has recently been discovered to assist cells in sensing and adapting to nutritional stress. This role of VGLL3 may confer a selective advantage during the evolution of placental mammals. However, the excessive activation of the VGLL3-mediated energy-sensing pathway can trigger inflammatory cell death and the exposure of self-antigens, leading to the onset of autoimmunity. These observations have raised the intriguing perspective that nutrient sensing serves as a double-edged sword in immune regulation. Mechanistically, VGLL3 intersects with Hippo signaling and activates multiple downstream, immune-associated genes that play roles in metabolic regulation. Understanding the multifaceted roles of VGLL3 in nutrient sensing and immune modulation provides insight into the fundamental question of sexual dimorphism in immunometabolism and sheds light on potential therapeutic targets for autoimmune diseases., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s), Published by Wolters Kluwer Health, Inc.)

Small intestinal satiation pathways involve nutrient-induced stimulation of chemoreceptors leading to release of satiety hormones from intestinal enteroendocrine cells (ECCs). Whether adaptations in these pathways contribute to increased maternal food intake during pregnancy is unknown. To determine the expression of intestinal nutrient-sensors and satiety hormone transcripts and proteins across pregnancy in mice. Female C57BL/6J mice (10–12 weeks old) were randomized to mating and then tissue collection at early- (6.5 d), mid- (12.5 d) or late-pregnancy (17.5 d), or to an unmated age matched control group. Relative transcript expression of intestinal fatty acid, peptide and amino acid and carbohydrate chemoreceptors, as well as gut hormones was determined across pregnancy. The density of G-protein coupled receptor 93 (GPR93), free fatty acid receptor (FFAR) 4, cholecystokinin (CCK) and glucagon-like peptide1 (GLP-1) immunopositive cells was then compared between non-pregnant and late-pregnant mice. Duodenal GPR93 expression was lower in late pregnant than non-pregnant mice (P < 0.05). Ileal FFAR1 expression was higher at mid- than at early- or late-pregnancy. Ileal FFAR2 expression was higher at mid-pregnancy than in early pregnancy. Although FFAR4 expression was consistently lower in late-pregnant than non-pregnant mice (P < 0.001), the density of FFAR4 immunopositive cells was higher in the jejunum of late-pregnant than non-pregnant mice. A subset of protein and fatty acid chemoreceptor transcripts undergo region-specific change during murine pregnancy, which could augment hormone release and contribute to increased food intake. Further investigations are needed to determine the functional relevance of these changes. • Adaptations in intestinal chemoreceptors and hormones during pregnancy is unknown. • Duodenal GPR93 and intestinal FFAR4 expression was lower in late-pregnant mice. • FFAR4 positive cells were greater in the jejunum of late- vs. non-pregnant mice. • Gut hormone (CCK & GLP-1) expression and cell density was unchanged in pregnancy. [ABSTRACT FROM AUTHOR]

Bitter taste is an aversive taste because it is unconsciously associated with toxic compounds. However, a considerable variability in bitter sensitivity exists in those who have the genetic polymorphism for bitter taste receptors (TAS2Rs). Besides the oral cavity, TAS2Rs are present in many body tissues, including the gastrointestinal tract; therefore, they are crucial players both in the gustatory/hedonic system and in the homeostatic system, triggering numerous biological responses, including adipogenesis, carcinogenesis, or immunity. Bitter-tasting compounds are widely distributed in plant and animal foods and belong to many chemical classes. In this study, the evidence was reviewed on bitter peptides, considering the food sources, their formation in food under different processing and storage conditions and in the gastrointestinal tract during digestion, as well as their biological activities. Bitterness associated with peptides is due to the presence of hydrophobic amino acids in the C-terminus. The current literature mainly explores the enzymes and hydrolysis conditions, with the aim of reducing the formation of bitter peptides in hydrolysate preparation or food. Few studies highlight the bioactivity (namely, antihypertensive, antidiabetic, antioxidant, or immunity boosting), besides the bitterness. However, encapsulation of bitter peptides has been tentatively used to develop antihypertensive and antidiabetic supplements. In the era of personalized nutrition and precision medicine, the evidence available suggests the opportunity to use bitter bioactive peptides as functional ingredients in food. Such types of food may modulate a plethora of physiological mechanisms by targeting TAS2Rs in the gastrointestinal tract, thus modulating appetite sensations or gastrointestinal motility and discomfort according to individual nutritional needs and goals. More studies are needed to optimize the technological strategies to target TAS2Rs by bitter bioactive peptides, improve their stability in food, and validate the biological efficacy through well-designed in vivo studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Cells continuously fine-tune signaling pathway proteins to match nutrient and stress levels in their local environment by modifying intracellular proteins with O-linked N-acetylglucosamine (O-GlcNAc) sugars, an essential process for cell survival and growth. The small size of these monosaccharide modifications poses a challenge for functional determination, but the chemistry and biology communities have together created a collection of precision tools to study these dynamic sugars. This review presents the major themes by which O-GlcNAc influences signaling pathway proteins, including G-protein coupled receptors, growth factor signaling, mitogen-activated protein kinase (MAPK) pathways, lipid sensing, and cytokine signaling pathways. Along the way, we describe in detail key chemical biology tools that have been developed and applied to determine specific O-GlcNAc roles in these pathways. These tools include metabolic labeling, O-GlcNAc-enhancing RNA aptamers, fluorescent biosensors, proximity labeling tools, nanobody targeting tools, O-GlcNAc cycling inhibitors, light-activated systems, chemoenzymatic labeling, and nutrient reporter assays. An emergent feature of this signaling pathway meta-analysis is the intricate interplay between O-GlcNAc modifications across different signaling systems, underscoring the importance of O-GlcNAc in regulating cellular processes. We highlight the significance of O-GlcNAc in signaling and the role of chemical and biochemical tools in unraveling distinct glycobiological regulatory mechanisms. Collectively, our field has determined effective strategies to probe O-GlcNAc roles in biology. At the same time, this survey of what we do not yet know presents a clear roadmap for the field to use these powerful chemical tools to explore cross-pathway O-GlcNAc interactions in signaling and other major biological pathways., Competing Interests: Conflict of interest The authors declare no potential conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Lysosomes are more than just cellular recycling bins; they play a crucial role in regulating key cellular functions. Proper lysosomal function is essential for growth pathway regulation, cell proliferation, and metabolic homeostasis. Impaired lysosomal function is associated with lipid storage disorders and neurodegenerative diseases. Lysosomes form extensive and dynamic close contacts with the membranes of other organelles, including the endoplasmic reticulum, mitochondria, peroxisomes, and lipid droplets. These membrane contacts sites (MCSs) are vital for many lysosomal functions. In this chapter, we will explore lysosomal MCSs focusing on the machinery that mediates these contacts, how they are regulated, and their functional implications on physiology and pathology., (Copyright © 2024. Published by Elsevier Inc.)