Amino Acid Uptake Research Articles

Three transporters, including the novel Gai1 permease, drive amino acid uptake in Histoplasma yeasts

ABSTRACT The dimorphic fungus Histoplasma capsulatum, which almost exclusively resides within host phagocytic cells during infection, must meet its nutritional needs by scavenging molecules from the phagosome environment. The requirement for gluconeogenesis, but not fatty acid catabolism, for intracellular growth, implicates amino acids as a likely intracellular nutrient source. Consequently, we investigated Histoplasma growth on amino acids. Growth assays demonstrated that Histoplasma yeasts readily utilize most amino acids as nitrogen sources but only efficiently catabolize glutamine, glutamate, aspartate, proline, isoleucine, and alanine as carbon sources. An amino acid permease-based conserved domain search identified 28 putative amino acid transporters within the Histoplasma genome. We characterized the substrate specificities of the major Histoplasma amino acid transporters using a Saccharomyces cerevisiae heterologous expression system and found that H. capsulatum Dip5, Gap3, and a newly described permease, Gai1, comprise most of Histoplasma’s amino acid import capacity. Histoplasma yeasts deficient in these three transporters are impaired for growth on free amino acids but proliferate within macrophages and remain fully virulent during infection of mice, indicating that free amino acids are not the principal nutrient source within the phagosome to support Histoplasma proliferation during infection.

Research progress on the function and regulatory pathways of amino acid permeases in fungi.

Nitrogen sources are pivotal for the formation of fungal mycelia and the biosynthesis of metabolites, playing a crucial role in the growth and development of fungi. Amino acids are integral to protein construction, constitute an essential nitrogen source for fungi. Fungi actively uptake amino acids from their surroundings, a process that necessitates the involvement of amino acid permeases (AAPs) located on the plasma membrane. By sensing the intracellular demand for amino acids and their extracellular availability, fungi activate or suppress relevant pathways to precisely regulate the genes encoding these transporters. This review aims to illustrate the function of fungal AAPs on uptake of amino acids and the effect of AAPs on fungal growth, development and virulence. Additionally, the complex mechanisms to regulate expression of aaps are elucidated in mainly Saccharomyces cerevisiae, including the Ssy1-Ptr3-Ssy5 (SPS) pathway, the Nitrogen Catabolite Repression (NCR) pathway, and the General Amino Acid Control (GAAC) pathway. However, the physiological roles of AAPs and their regulatory mechanisms in other species, particularly pathogenic fungi, merit further exploration. Gaining insights into these aspects could reveal how AAPs facilitate fungal adaptation and survival under diverse stress conditions, shedding light on their potential impact on fungal biology and pathogenicity.

Transport of Neutral Amino Acids in the Jejunum of Pigs with Special Consideration of L-Methionine

Background: Methionine (Met) is a popular nutritional supplement in humans and animals. It is routinely supplemented to pigs as L-Met, DL-Met, or DL-2-hydroxy-4-(methylthio) butanoic acid (DL-HMTBA). Methods: We investigated the effect of these Met supplements on jejunal amino acid (AA) transport in male castrated Piétrain × Danbred pigs, also including a non-supplemented group. The mucosal-to-serosal flux of ten [14C]-labeled AAs (L-glutamine, glycine, L-leucine, L-lysine, L-Met, L-serine, L-threonine, L-tryptophan, L-tyrosine and L-valine) was investigated at two concentrations (50 µM and 5 mM). Inhibition of apical uptake by mucosal L-Met was also measured for these AAs. The intestinal expression of apical AA transporters, angiotensin-converting enzyme II and inflammation-related genes were compared with those of a previous study. Results: Except for tryptophan and lysine at 5 mM, all AA fluxes were Na+-dependent (p ≤ 0.05), and the uptake of most AAs, except glycine and lysine, was inhibited by L-Met (p < 0.001). A correlation network existed between Na+-dependent fluxes of most AAs (except tryptophan and partly glycine). We observed the upregulation of B0AT1 (SLC6A19) (p < 0.001), the downregulation of ATB0,+ (SLC6A14) (p < 0.001) and a lower expression of CASP1, IL1β, IL8, TGFβ and TNFα in the present vs. the previous study (p < 0.001). Conclusions: The correlating AAs likely share the same Na+-dependent transporter(s). A varying effect of the Met supplement type on AA transport in the two studies might be related to a different level of supplementation or a different inflammatory status of the small intestine.

Solute carrier transporters-mediated amino acid uptake is essential for thermogenic activation of human primary adipocytes

Solute carrier transporters-mediated amino acid uptake is essential for thermogenic activation of human primary adipocytes

Contrasting responses of gross N transformation to oxalic acid and glucose supplement in paddy soil

Labile organic carbon (C) substrates could accelerate microbial transformation of soil N pool by stimulating the decomposition of large molecule organic N. However, it remains unclear how gross N transformation processes (protein depolymerization, amino acid uptake, microbial N mineralization and NH4+-N uptake rates) in response to individual C substrates. Typical paddy soil was incubated with the supplement of organic acid or glucose under simulated field water conditions for 16 days to assess the gross N transformation rates by 15N pool dilution assays. A mixture of 15N labeled amino acid was applied to gross protein depolymerization and amino acid uptake rates measurement, and 15N-(NH4)2SO4 was used to gross microbial N mineralization and NH4+-N uptake rates analyses. Oxalic acid supplement promoted the gross protein depolymerization, gross microbial uptake of amino acid, and gross N mineralization rates at the early stage, since oxalic acid supplement urged microbes to decompose large molecular organic N to acquire amino acid derived C and excluded the superfluous N via mineralization as evidenced by the increase of NH4+-N. By contrast, glucose supplement diminished the gross N transformation processes, since microbes prefer to utilize the native NH4+-N to meet their N demand, which was supported by the decreasing NH4+-N concentration in soil, and consequently decrease the decomposition for the large molecule organic N. With the increase of microbial growth, especially for bacteria, glucose amendment stimulated the large molecular organic N depolymerization to acquire amino acid to maintain the microbial C/N stoichiometric balance. Compared to glucose treatment, oxalic acid supplement stimulated more N allocation into microbial growth but not for mineralization, and thus led to higher microbial N use efficiency, which was adverse for available inorganic N supply for rice growth in paddy ecosystem. Overall, this study emphasizes that low molecular organic C substrates of organic acid and glucose exerted contrasting influences on gross N transformation, and help to improve our understanding of the mechanism of the coupling biotransformation of C and N in paddy soil.

The Use of Patient-Derived Organoids in the Study of Molecular Metabolic Adaptation in Breast Cancer

Around 13% of women will likely develop breast cancer during their lifetime. Advances in cancer metabolism research have identified a range of metabolic reprogramming events, such as altered glucose and amino acid uptake, increased reliance on glycolysis, and interactions with the tumor microenvironment (TME), all of which present new opportunities for targeted therapies. However, studying these metabolic networks is challenging in traditional 2D cell cultures, which often fail to replicate the three-dimensional architecture and dynamic interactions of real tumors. To address this, organoid models have emerged as powerful tools. Tumor organoids are 3D cultures, often derived from patient tissue, that more accurately mimic the structural and functional properties of actual tumor tissues in vivo, offering a more realistic model for investigating cancer metabolism. This review explores the unique metabolic adaptations of breast cancer and discusses how organoid models can provide deeper insights into these processes. We evaluate the most advanced tools for studying cancer metabolism in three-dimensional culture models, including optical metabolic imaging (OMI), matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), and recent advances in conventional techniques applied to 3D cultures. Finally, we explore the progress made in identifying and targeting potential therapeutic targets in breast cancer metabolism.

The impact of cellulose nanocrystals on the properties of poly(2‐hydroxyethyl methacrylate)‐based contact lenses

AbstractContact lenses are widely used corrective devices for addressing vision impairments. In addition to their traditional role, these lenses are increasingly applied in personalized care, biosensing, and drug release, thus broadening their application as multifunctional devices. Nanoparticles are often used to introduce new functionalities to these materials. In this context, the role played by different nanoparticles requires attention to ensure that lens manufacture and patient comfort meet the desired criteria. This study investigates the properties of contact lenses prepared by incorporating cellulose nanocrystals into the poly(2‐hydroxyethyl methacrylate) matrix. Using photopolymerization reactions, polyHEMA‐based lenses and nanocomposites containing freeze‐dried and never‐dried nanoparticles were obtained. Fundamental properties of these lenses were evaluated to verify whether the nanoparticles could have a negative effect on the materials. Subsequently, the potential impact of these nanoparticles on the adsorption of model amino acids was investigated. Our findings reveal that the presence of cellulose nanocrystals modifies on lens thickness, light transmittance, mechanical properties, refractive index (RI), and the uptake of amino acids by the contact lenses. This could potentially affect patient comfort and modify the uptake and release of pharmaceutical ingredients by the material. Additionally, it could impact how these materials interact with biomolecules present in the lacrimal fluid.

Increasing plant species diversity benefits soil protein accumulation in a subtropical forest

Abstract Protein, derived from plant and microbial residues, constitutes a significant portion of soil nitrogen or organic carbon pool and plays a crucial role in determining soil nitrogen and carbon sequestration. Though diversifying plant species has been regarded as a promising strategy for promoting soil nitrogen or organic carbon accumulation during vegetation restoration or afforestation, how increasing plant species diversity (PSD) would influence soil protein pool remains unknown. We selected 45 plots covering a natural gradient of PSD, which was reflected by the Shannon index and varied from 0.15 to 3.57, in a subtropical karst forest. The major objective was to investigate the impact of increasing PSD on soil protein abundance, with soil protein depolymerization rate and multiple biotic and abiotic variables being measured to explore the underlying mechanism. The relative abundance of soil protein, that is proportion in soil organic matter varied between 24.1 and 34.0% with an average of 29.2 ± 2.3% across the 45 plots. Soil protein abundance increased on average by 1.56% with each unit of PSD increase. Nevertheless, soil protease activity, protein depolymerization rate and microbial amino acid uptake rate all significantly (p < 0.05) decreased as PSD increased. The mechanism underlying the increase of soil protein abundance in response to higher PSD included three aspects, that is stimulating microbial biomass and subsequent microbial residue input to the soil, promoting mineral protection of soil protein via elevating levels of soil exchangeable calcium and magnesium, and decreasing soil protease activity and protein depolymerization due to aggravated soil microbial phosphorus limitation. Synthesis and application: Our study suggests that increasing PSD is an efficient way to promote soil protein accumulation. Given that protein is a major component of soil nitrogen or organic carbon pool, diversifying plant species during vegetation restoration or afforestation would hence benefit soil nitrogen and organic carbon sequestration.

Transcriptomic analysis provides insights into the mechanisms underlying the resistance of Penaeus vannamei to Enterocytozoon hepatopenaei (EHP)

The Penaeus vannamei aquaculture industry is facing a significant challenge in the form of hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP), resulting in substantial economic losses. However, the extent of knowledge regarding the mechanisms by which shrimp resist EHP is limited. We screened resistant and susceptible shrimp and found that resistant shrimp had lower EHP load and less tissue damage. To gain insight into the molecular mechanisms underlying the EHP resistance of shrimp, a comparison was conducted at the transcriptional level between the resistant and susceptible families. Transcriptomic analysis of shrimp hepatopancreas revealed significant differences between the resistant and susceptible families. Compared to the susceptible family, the immune system of the resistant family was activated. The resistant family showed up-regulation in the expression of cathepsin L, C-type lectin, penaeidin, chitinase genes, and metabolism of xenobiotics by cytochrome P450-related genes. Additionally, the resistant shrimp exhibited a higher capacity for amino acid uptake. The observed differences in the resistant and susceptible family transcriptome may contribute to the shrimp's resistance to EHP.

Utilization efficiency of Ehrlich pathway-related amino acid affected higher alcohol acetate production of non-Saccharomyces yeasts during alcoholic fermentation

Non-Saccharomyces yeasts have attracted great oenological interest due to their contribution to wine aroma, while the underlying mechanisms remain complex and insufficiently understood. To elucidate the potential mechanisms responsible for the high fruity esters production by P. kluyveri PK-19, a non-Saccharomyces yeast strain known for its aroma production, the nitrogen assimilation profile, fermentation capacity, and volatile production were compared with those of three other yeast strains, namely Saccharomyces cerevisiae SC-19, Pichia fermentans Z9Y-3, and Hanseniaspora uvarum Yun268. Despite the intermediate fermentation capacity, P. kluyveri PK-19 showed strong nitrogen consumption and rapid uptake of Ehrlich pathway-related amino acids during the early stages of alcoholic fermentation. Moreover, P. kluyveri demonstrated a high efficiency in converting Ehrlich pathway-related amino acids into their corresponding higher alcohol acetates (HAAs), indicating an enhanced ability to synthesize HAAs from Ehrlich pathway precursors. The rapid assimilation of Ehrlich pathway-related amino acids and efficient transformation to HAAs potentially contributed to the high production of HAAs in P. kluyveri PK-19. These results suggest that supplementing P. kluyveri-involved fermentation with Ehrlich pathway-related amino acids can increase HAA production and modify wine aroma profiles.

The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of Saccharomyces cerevisiae to glucose

Cellular organelles maintain areas of close apposition with other organelles at which the cytosolic gap in between them is reduced to a minimum. These membrane contact sites (MCS) are vital for organelle communication and are formed by molecular tethers that physically connect opposing membranes. Although many regulatory pathways are known to converge at MCS, a link between MCS and transcriptional regulation-the primary mechanism through which cells adapt their metabolism to environmental cues-remains largely elusive. In this study, we performed RNA-sequencing on Saccharomyces cerevisiae cells lacking tricalbin proteins (Tcb1, Tcb2, and Tcb3), a family of tethering proteins that connect the endoplasmic reticulum with the plasma membrane and Golgi, to investigate if gene expression is altered when MCS are disrupted. Our results indicate that in the tcb1Δ2Δ3Δ strain, pathways responsive to a high-glucose environment, including glycolysis, fermentation, amino acid synthesis, and low-affinity glucose uptake, are upregulated. Conversely, pathways crucial during glucose depletion, such as the tricarboxylic acid cycle, respiration, high-affinity glucose uptake, and amino acid uptake are downregulated. In addition, we demonstrate that the altered gene expression of tcb1Δ2Δ3Δ in glucose metabolism correlates with increased growth, glucose consumption, CO2 production, and ethanol generation. In conclusion, our findings reveal that tricalbin protein deletion induces a shift in gene expression patterns mimicking cellular responses to a high-glucose environment. This suggests that MCS play a role in sensing and signaling pathways that modulate gene transcription in response to glucose availability.

Maternal gut Bifidobacterium breve modifies fetal brain metabolism in germ-free mice

BackgroundRecent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. ObjectiveThis study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. MethodsGerm-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. ResultsMaternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. ConclusionsThe presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.

Replacing Cereal with Ultraprocessed Foods in Pig Diets Does Not Adverse Gut Microbiota, L-glutamate Uptake, or Serum Insulin

BackgroundUsing ultraprocessed food (UPF) to replace traditional feed ingredients offers a promising strategy for enhancing food production sustainability. ObjectiveTo analyze the impact of salty and sugary UPF on gut microbiota, amino acids uptake, and serum analytes in growing and finishing pig. MethodsThirty-six Swiss Large White male castrated pigs were assigned to 3 experimental diets: 1) standard (ST), 0% UPF; 2) 30% conventional ingredients replaced by sugary (SU) UPF; and 3) 30% conventional ingredients replaced by salty (SA) UPF. The next-generation sequencing was used to characterize the fecal microbiota. Transepithelial electrical resistance and the active uptake of selected amino acids in pig jejuna were also evaluated. Data were enriched with measurements of fecal volatile fatty acids and serum urea, minerals, and insulin. All data analyses were run in R v4.0.3. The packages phyloseq, vegan, microbiome, and microbiomeutilities were used for microbiota data analysis. The remaining data were analyzed by analysis of variance using linear mixed-effects regression models. ResultsThe UPF did not affect fecal microbiota abundance or biodiversity. The Firmicutes to Bacteroidetes ratio remained unaffected. SU-induced increase in the Anaerostipes genus suggested altered glucose metabolism, whereas SA increased the abundance of CAG-352 and p-2534-18B. No effects on fecal volatile fatty acids were observed. Assumptions of UPF negatively affecting small intestinal physiology were not supported by the measurements of transepithelial electrical resistance in pigs. Active amino acids uptake tests showed potential decrease in L-glutamate absorption in the SA compared with the SU diet. Blood serum analysis indicated no adverse effects on urea, calcium, magnesium, or potassium concentration but the SU group resulted in a lower blood serum insulin concentration at the time of blood collection. ConclusionsWhen incorporated at 30% into a standard growing finishing diet for pigs, UPF does not have detrimental effects on gut microbiota, intestinal integrity, and blood mineral homeostasis.

Amino acid permease OsAAP12 negatively regulates rice tillers and grain yield by transporting specific amino acids to affect nitrogen and cytokinin pathways

Amino acids are necessary nutrients for the growth of Oryza sativa (rice), which can be mediated by amino acid transporter; however, our understanding of these transporters is still limited. This study found that the expression levels of amino acid permease gene OsAAP12 differed between indica and japonica rice. Altered expression of OsAAP12 negatively regulated tillering and yield in transgenic rice lines. Subcellular localization revealed that OsAAP12 was primarily localized to the plasma membrane. Moreover, it was indicated that OsAAP12 transported polar neutral amino acids asparagine (Asn), threonine (Thr), and serine (Ser) through experiments involving yeast heterologous complementation, fluorescence amino acid uptake, and amino acid content determination. Additionally, exogenous application of amino acids Asn, Thr, and Ser suppressed axillary buds outgrowth in OsAAP12 overexpression lines compared with wild-type ZH11. Conversely, the opposite trend was observed in CRISPR mutant lines. RNA-seq analysis showed that the expression patterns of genes involved in the nitrogen and cytokinin pathways were generally altered in OsAAP12 modified lines. Hormone assays indicated that OsAAP12 mutant lines accumulated cytokinins in the basal part of rice, whereas overexpression lines had the opposite effect. In summary, CRISPR mutant of OsAAP12 boosted rice tillering and grain yield by coordinating the content of amino acids and cytokinins, which has potential application value in high-yield rice breeding.

Dietary protein splanchnic uptake and digestibility via stable isotope tracers.

Dietary proteins are broken down into peptides across the gastrointestinal tract, with skeletal muscle being a primary deposition site for amino acids in the form of incorporation into, for example, metabolic and structural proteins. It follows that key research questions remain as to the role of amino acid bioavailability, of which protein digestibility and splanchnic sequestration (absorption and utilization) of amino acids are determining factors, impact upon muscle protein synthesis (MPS) in clinical states. Elevated splanchnic amino acid uptake has been implicated in anabolic resistance (i.e. attenuated anabolic responses to protein intake) observed in ageing, though it is unclear whether this limits MPS. The novel 'dual stable isotope tracer technique' offers a promising, minimally invasive approach to quantify the digestion of any protein source(s). Current work is focused on the validation of this technique against established methods, with scope to apply this to clinical and elderly populations to help inform mechanistic and interventional insights. Considerations should be made for all facets of protein quality; digestibility of the protein, absorption/utilization and subsequent peripheral bioavailability of amino acids, and resultant stimulation of MPS. Stable isotope tracer techniques offer a minimally invasive approach to achieve this, with wide-ranging clinical application.

Clostridial Myonecrosis: A Comprehensive Review of Toxin Pathophysiology and Management Strategies.

Clostridial myonecrosis, commonly known as gas gangrene (GG), is a rapidly progressing and potentially fatal bacterial infection that primarily affects muscle and soft tissue. In the United States, the incidence of GG is roughly 1000 cases per year, while, in developing countries, the incidence is higher. This condition is most often caused by Clostridium perfringens, a Gram-positive, spore-forming anaerobic bacterium widely distributed in the environment, although other Clostridium species have also been reported to cause GG. The CP genome contains over 200 transport-related genes, including ABC transporters, which facilitate the uptake of sugars, amino acids, nucleotides, and ions from the host environment. There are two main subtypes of GG: traumatic GG, resulting from injuries that introduce Clostridium spores into deep tissue, where anaerobic conditions allow for bacterial growth and toxin production, and spontaneous GG, which is rarer and often occurs in immunocompromised patients. Clostridium species produce various toxins (e.g., alpha, theta, beta) that induce specific downstream signaling changes in cellular pathways, causing apoptosis or severe, fatal immunological conditions. For example, the Clostridium perfringens alpha toxin (CPA) targets the host cell's plasma membrane, hydrolyzing sphingomyelin and phosphatidylcholine, which triggers necrosis and apoptosis. The clinical manifestations of clostridial myonecrosis vary. Some patients experience the sudden onset of severe pain, swelling, and muscle tenderness, with the infection progressing rapidly to widespread tissue necrosis, systemic toxicity, and, if untreated, death. Other patients present with discharge, pain, and features of cellulitis. The diagnosis of GG primarily involves clinical evaluation, imaging studies such as X-rays, computer tomography (CT) scans, and culture. The treatment of GG involves surgical exploration, broad-spectrum antibiotics, antitoxin, and hyperbaric oxygen therapy, which is considered an adjunctive treatment to inhibit anaerobic bacterial growth and enhance the antibiotic efficacy. Early recognition and prompt, comprehensive treatment are critical to improving the outcomes for patients affected by this severe and life-threatening condition.

Irisin promotes tilapia muscle cell growth and amino acid uptake via IGF-1 signaling.

Irisin is a recently discovered myokine that facilitates the browning of white adipose tissue, increases glucose uptake in skeletal muscle, and influences metabolic processes in the liver. However, its potential effects on amino acid absorption remained largely unexplored. This study aimed to elucidate the role of irisin in modulating amino acid uptake and delineate the underlying molecular mechanisms involved. To this end, juvenile tilapia were administered intraperitoneal irisin injections at 100 ng/g body weight over 8 weeks. Evaluation of various physiological parameters revealed that irisin supplementation significantly improved the specific growth rate and feed conversion efficiency while reducing feed consumption. Muscle tissue analysis revealed that irisin significantly modified the proximate composition by increasing protein content and reducing lipid levels. It also significantly raised the levels of both essential and non-essential amino acids in the muscle. Histological analysis demonstrated that irisin-stimulated muscle growth through hyperplasia rather than hypertrophy, corroborated by upregulated IGF-1 mRNA and downregulated myostatin mRNA expression. Mechanistic studies in cultured tilapia muscle cells elucidated that irisin activated integrin receptors on muscle cells, which subsequently engaged IGF-1/IGF-1R signaling. Downstream of IGF-1R activation, irisin simultaneously stimulates the ERK1/2 and PI3K/mTORC2/Akt pathways. The convergence of these pathways upregulates L-type amino acid transporter 1 expression, thereby augmenting amino acid uptake into muscle cells. In summary, irisin supplementation in tilapia leads to improved muscle growth, predominantly via hyperplasia and augmented amino acid assimilation, governed by intricate cellular signaling pathways. These findings provide valuable aquaculture applications and novel insights into muscle development.

Principal role of fungi in soil carbon stabilization during early pedogenesis in the high Arctic

Climate warming is causing widespread deglaciation and pioneer soil formation over glacial deposits. Melting glaciers expose rocky terrain and glacial till sediment that is relatively low in biomass, oligotrophic, and depleted in nutrients. Following initial colonization by microorganisms, glacial till sediments accumulate organic carbon and nutrients over time. However, the mechanisms driving soil nutrient stabilization during early pedogenesis after glacial retreat remain unclear. Here, we traced amino acid uptake by microorganisms in recently deglaciated high-Arctic soils and show that fungi play a critical role in the initial stabilization of the assimilated carbon. Pioneer basidiomycete yeasts were among the predominant taxa responsible for carbon assimilation, which were associated with overall high amino acid use efficiency and reduced respiration. In intermediate- and late-stage soils, lichenized ascomycete fungi were prevalent, but bacteria increasingly dominated amino acid assimilation, with substantially decreased fungal:bacterial amino acid assimilation ratios and increased respiration. Together, these findings demonstrate that fungi are important drivers of pedogenesis in high-Arctic ecosystems that are currently subject to widespread deglaciation from global warming.

Cancer EV stimulate endothelial glycolysis to fuel protein synthesis via mTOR and AMPKα activation.

Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance and has profound effects on cellular metabolism. As such, hypoxia is an important contributor to cancer progression and is associated with a poor prognosis. Metabolic alterations in cells within the tumour microenvironment support tumour growth via, amongst others, the suppression of immune reactions and the induction of angiogenesis. Recently, extracellular vesicles (EV) have emerged as important mediators of intercellular communication in support of cancer progression. Previously, we demonstrated the pro-angiogenic properties of hypoxic cancer cell derived EV. In this study, we investigate how (hypoxic) cancer cell derived EV mediate their effects. We demonstrate that cancer derived EV regulate cellular metabolism and protein synthesis in acceptor cells through increased activation of mTOR and AMPKα. Using metabolic tracer experiments, we demonstrate that EV stimulate glucose uptake in endothelial cells to fuel amino acid synthesis and stimulate amino acid uptake to increase protein synthesis. Despite alterations in cargo, we show that the effect of cancer derived EV on recipient cells is primarily determined by the EV producing cancer cell type rather than its oxygenation status.

Amino acid metabolic reprogramming in the tumor microenvironment and its implication for cancer therapy.

Amino acids are essential building blocks for proteins, crucial energy sources for cell survival, and key signaling molecules supporting the resistant growth of tumor cells. In tumor cells, amino acid metabolic reprogramming is characterized by the enhanced uptake of amino acids as well as their aberrant synthesis, breakdown, and transport, leading to immune evasion and malignant progression of tumor cells. This article reviews the altered amino acid metabolism in tumor cells and its impact on tumor microenvironment, and also provides an overview of the current clinical applications of amino acid metabolism. Innovative drugs targeting amino acid metabolism hold great promise for precision and personalized cancer therapy.