TRIM2 promotes metabolic adaptation to glutamine deprivation via enhancement of CPT1A activity.

Cancer cells undergo metabolic adaptation to promote their survival and growth under energy stress conditions, yet the underlying mechanisms remain largely unclear. Here, we report that tripartite motif-containing protein 2 (TRIM2) is upregulated in response to glutamine deprivation by the transcription factor cyclic AMP-dependent transcription factor (ATF4). TRIM2 is shown to specifically interact with carnitine O-palmitoyltransferase 1 (CPT1A), a rate-limiting enzyme of fatty acid oxidation. Via this interaction, TRIM2 enhances the enzymatic activity of CPT1A, thereby regulating intracellular lipid levels and protecting cells from glutamine deprivation-induced apoptosis. Furthermore, TRIM2 is able to promote both in vitro cell proliferation and in vivo xenograft tumor growth via CPT1A. Together, these findings establish TRIM2 as an important regulator of the metabolic adaptation of cancer cells to glutamine deprivation and implicate TRIM2 as a potential therapeutic target for cancer.

The integrated stress response promotes neural stem cell survival under conditions of mitochondrial dysfunction in neurodegeneration.

Impaired mitochondrial function is a hallmark of aging and a major contributor to neurodegenerative diseases. We have shown that disrupted mitochondrial dynamics typically found in aging alters the fate of neural stem cells (NSCs) leading to impairments in learning and memory. At present, little is known regarding the mechanisms by which neural stem and progenitor cells survive and adapt to mitochondrial dysfunction. Using Opa1-inducible knockout as a model of aging and neurodegeneration, we identify a decline in neurogenesis due to impaired stem cell activation and progenitor proliferation, which can be rescued by the mitigation of oxidative stress through hypoxia. Through sc-RNA-seq, we identify the ATF4 pathway as a critical mechanism underlying cellular adaptation to metabolic stress. ATF4 knockdown in Opa1-deficient NSCs accelerates cell death, while the increased expression of ATF4 enhances proliferation and survival. Using a Slc7a11 mutant, an ATF4 target, we show that ATF4-mediated glutathione production plays a critical role in maintaining NSC survival and function under stress conditions. Together, we show that the activation of the integrated stress response (ISR) pathway enables NSCs to adapt to metabolic stress due to mitochondrial dysfunction and metabolic stress and may serve as a therapeutic target to enhance NSC survival and function in aging and neurodegeneration.

Dynamic indicators of acute respiratory diseases treatment in children after correction.

OBJECTIVE: Aim: To study the Respiratory pathology of the upper respiratory tract, markers of the inflammatory response of the organism, Oxidative stress, Metabolic adaptation and possibilities of correction. PATIENTS AND METHODS: Materials and Methods: The study group (n=111) included school-aged children (10-14 years old). The general group of inflammatory diseases of the respiratory tract (J000-J06) was considered, with a diagnosis of acute respiratory infection (ARI) of viral and bacterial origin and included local inflammationof the upper respiratory tract with presentation of acute pharyngitis (68.0%), acute bronchitis (22,0%), acute tonsillitis (10,0%). RESULTS: Results: Dynamic observation of groups of children who received optimized (group 1, n=60) and basic (group 2, n=51) treatment was carried out. The level of the erythrocyte pool correlated with IL-1 (r=-0,29, p=0,03), IL-4 (r=0,32, p=0,01), TNF-α (r=-0,35 , p=0,006). Creatinine value correlated with IL-10 (r=0,3, p=0,005), γ-IFN (r=0,42, p=0,001), TNF-α (r=0,25, p=0,05). Correlations of ferritin presented positive correlation values with the level of total protein (r=0,26, p=0,04) and TNF-α (r=0,41, p=0,001). CONCLUSION: Conclusions: After the optimized treatment, there was a significant decrease in the reliable levels of CRP and γ-IFN by 7 and 4,4 times (by groups) and 5,8 and 3,2 times (by groups), respectively. Correlation relationships of urea levels with IL-2,4 were detected. The level of the erythrocyte pool correlated with IL-1,4, TNF-α, Ferritin presented positive correlation values with the level of total protein,TNF-α .

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Mitochondrial-dependent oxidative phosphorylation is key for postnatal metabolic adaptation of alveolar macrophages in the lung.

Alveolar macrophages (AMs) seed in lung during embryogenesis and become mature in perinatal period. Establishment of acclimatization to environmental challenges is important, whereas the detailed mechanisms that drive metabolic adaptation of AMs remains to be elucidated. Here, we showed that energy metabolism of AMs was transformed from glycolysis prenatally to oxidative phosphorylation (OXPHOS) postnatally accompanied by up-regulated expression of mitochondrial transcription factor A (TFAM). TFAM deficiency disturbed mitochondrial stability and decreased OXPHOS, which finally impaired AM maintenance and function, but not AM embryonic development. Mechanistically, Tfam-deletion resulted in impaired mitochondrial respiration and decreased ATP production, which triggered endoplasmic reticulum (ER) stress to cause B cell lymphoma 2 ovarian killer (BOK) accumulation and abnormal distribution of intracellular Ca2+, eventually led to induce AM apoptotic death. Thus, our data illustrated mitochondrial-dependent OXPHOS played a key role in orchestrating AM postnatal metabolic adaptation.

Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut.

Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC with essential roles in infections and tissue repair, but how they adapt to the gut environment to maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3 maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resulting in defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression of Hexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinases in glycolysis, Tox2-/- ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopic expression of Hexokinase-2 rescued Tox2-/- gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environments by programming glycolytic metabolism. Our results reveal the requirement for Tox2 to support the metabolic adaptation of ILC3 within the gastrointestinal tract.

Remodelling of mitochondrial function by import of specific lipids at multiple membrane-contact sites.

Organelles form physical and functional contact between each other to exchange information, metabolic intermediates, and signaling molecules. Tethering factors and contact site complexes bring partnering organelles into close spatial proximity to establish membrane contact sites (MCSs), which specialize in unique functions like lipid transport or Ca2+ signaling. Here, we discuss how MCSs form dynamic platforms that are important for lipid metabolism. We provide a perspective on how import of specific lipids from the ER and other organelles may contribute to remodeling of mitochondria during nutrient starvation. We speculate that mitochondrial adaptation is achieved by connecting several compartments into a highly dynamic organelle network. The lipid droplet appears to be a central hub in coordinating the function of these organelle neighborhoods.

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila.

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.

Influence of Heat Stress on Body Surface Temperature and Blood Metabolic, Endocrine, and Inflammatory Parameters and Their Correlation in Cows.

This study aimed to determine whether heat stress affected the values and correlations of metabolic, endocrinological, and inflammatory parameters as well as the rectal and body surface temperature of cows in the early and middle stages of lactation. This experiment was conducted in May (thermoneutral period), June (mild heat stress), and July (moderate to severe heat stress). In each period we included 15 cows in early lactation and 15 in mid-lactation. The increase in rectal and body surface temperatures (°C) in moderate to severe heat stress compared to the thermoneutral period in different regions was significant (p < 0.01) and the results are presented as mean and [95%CI]: rectal + 0.9 [0.81-1.02], eye + 6 [5.74-6.25], ear + 13 [11.9-14.0], nose + 3.5 [3.22-3.71], forehead + 6.6 [6.43-6.75], whole head + 7.5 [7.36-7.68], abdomen + 8.5 [8.25-8.77], udder + 7.5 [7.38-7.65], front limb + 6 [5.89-6.12], hind limb + 3.6 [3.46-3.72], and whole body + 9 [8.80-9.21]. During heat stress (in both mild and moderate to severe stress compared to a thermoneutral period), an increase in the values of extracellular heat shock protein 70 (eHsp70), tumor necrosis factor α (TNFα), cortisol (CORT), insulin (INS), revised quantitative insulin sensitivity check index (RQUICKI), urea, creatinine, total bilirubin, aspartate transpaminase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and creatin kinase (CK) occurred, as well as a decrease in the values of triiodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA), glucose (GLU), ß-Hydroxybutyrate (BHB), calcium, phosphorus, total protein (TPROT), albumin (ALB), triglycerides (TGCs), and cholesterol (CHOL). In cows in early lactation compared to cows in mid-lactation, there was a significantly larger increase (p < 0.01) in the values of eHsp70, TNFα, GLU, RQUICKI, and GGT, while the INS increase was smaller during the three experimental periods. The decrease in the values of Ca, CHOL, and TGC was more pronounced in cows in early lactation compared to cows in mid-lactation during the three experimental periods. Rectal temperature was related to eHsp70 (r = 0.38, p < 0.001) and TNFα (r = 0.36, p < 0.01) and showed non-significant poor correlations with other blood parameters. Blood parameters correlate with body surface temperature, with the following most common results: eHsp70 and TNFα showed a moderately to strongly significant positive correlation (r = 0.79-0.96, p < 0.001); CORT, INS, and Creat showed fairly to moderately significant positive correlations; T3, T4, NEFA and GLU showed fairly to moderately significant negative correlations (r = 0.3-0.79; p < 0.01); RQUICKI, urea, AST, and GGT showed fairly and significantly positive correlations; and TGC, CHOL, TPROT, and ALB showed fairly and significantly negative correlations (r = 0.3-0.59; p < 0.01). Measuring the surface temperature of the whole body or head can be a useful tool in evaluating the metabolic response of cows because it has demonstrated an association with inflammation (TNFα, eHsp70), endocrine response (CORT, T3, T4), the increased use of glucose and decreased use of lipids for energy purposes (INS, NEFA, GLU, and RQUICKI), and protein catabolism (ALB, TPROT, urea, Creat), which underlies thermolysis and thermogenesis in cows under heat stress. In future research, it is necessary to examine the causality between body surface area and metabolic parameters.

Effects of intermittent dieting with break periods on body composition and metabolic adaptation: a systematic review and meta-analysis.

CONTEXT: Intermittent dieting incorporated with break periods (INT-B) has recently been promoted as an alternative dietary approach for optimal weight management. OBJECTIVE: This study assessed the effectiveness of INT-B compared with that of conventional continuous energy restriction (CER) for improving body composition and attenuating metabolic adaptation. DATA SOURCES: A systematic search was conducted on 6 databases using all available records until July 2023. DATA EXTRACTION: The extracted data included the lead author, year of publication, population characteristics, intervention protocols, duration, and adherence. DATA ANALYSIS: Random-effects meta-analyses were conducted for within-group and between-group comparisons of anthropometric and metabolic outcomes. Subgroup moderator analysis was performed for the types of INT-B, intervention duration, and population characteristics. RESULTS: Of the 1469 records, 12 randomized trials (with 881 participants) were included. Within-group analyses demonstrated significant improvements in body mass, fat mass, body mass index, body fat percentage, and waist circumference following both INT-B and CER, with no significant group differences. However, resting metabolic rate (RMR) was significantly reduced following CER only. The compensatory reduction in RMR was significantly smaller following INT-B compared with CER, suggesting a lesser degree of metabolic adaptation. INT-B had a more significant effect on RMR retention in individuals with overweight/obesity compared with resistance-trained individuals. CONCLUSION: This review provides up-to-date evidence for INT-B as a viable dietary strategy to improve body composition and attenuate metabolic adaptation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023448959.

Unraveling stress resilience: Insights from adaptations to extreme environments by Astyanax mexicanus cavefish.

Extreme environmental conditions have profound impacts on shaping the evolutionary trajectory of organisms. Exposure to these conditions elicits stress responses, that can trigger phenotypic changes in novel directions. The Mexican Tetra, Astyanax mexicanus, is an excellent model for understanding evolutionary mechanisms in response to extreme or new environments. This fish species consists of two morphs; the classical surface-dwelling fish and the blind cave-dwellers that inhabit dark and biodiversity-reduced ecosystems. In this review, we explore the specific stressors present in cave environments and examine the diverse adaptive strategies employed by cave populations to not only survive but thrive as successful colonizers. By analyzing the evolutionary responses of A. mexicanus, we gain valuable insights into the genetic, physiological, and behavioral adaptations that enable organisms to flourish under challenging environmental conditions.

Ultrastructural, Antioxidant, and Metabolic Responses of Male Genetically Improved Farmed Tilapia (GIFT, Oreochromis niloticus) to Acute Hypoxia Stress.

Tilapia tolerate hypoxia; thus, they are an excellent model for the study of hypoxic adaptation. In this study, we determined the effect of acute hypoxia stress on the antioxidant capacity, metabolism, and gill/liver ultrastructure of male genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Fish were kept under control (dissolved oxygen (DO): 6.5 mg/L) or hypoxic (DO: 1.0 mg/L) conditions for 72 h. After 2 h of hypoxia stress, antioxidant enzyme activities in the heart and gills decreased, while the malondialdehyde (MDA) content increased. In contrast, in the liver, antioxidant enzyme activities increased, and the MDA content decreased. From 4 to 24 h of hypoxia stress, the antioxidant enzyme activity increased in the heart but not in the liver and gills. Cytochrome oxidase activity was increased in the heart after 4 to 8 h of hypoxia stress, while that in the gills decreased during the later stages of hypoxia stress. Hypoxia stress resulted in increased Na+-K+-ATP activity in the heart, as well as hepatic vacuolization and gill lamella elongation. Under hypoxic conditions, male GIFT exhibit dynamic and complementary regulation of antioxidant systems and metabolism in the liver, gills, and heart, with coordinated responses to mitigate hypoxia-induced damage.

Metabolic adaptations of Microbacterium sediminis YLB-01 in deep-sea high-pressure environments.

The deep-sea environment is an extremely difficult habitat for microorganisms to survive in due to its intense hydrostatic pressure. However, the mechanisms by which these organisms adapt to such extreme conditions remain poorly understood. In this study, we investigated the metabolic adaptations of Microbacterium sediminis YLB-01, a cold and stress-tolerant microorganism isolated from deep-sea sediments, in response to high-pressure conditions. YLB-01 cells were cultured at normal atmospheric pressure and 28 ℃ until they reached the stationary growth phase. Subsequently, the cells were exposed to either normal pressure or high pressure (30 MPa) at 4 ℃ for 7 days. Using NMR-based metabolomic and proteomic analyses of YLB-01 cells exposed to high-pressure conditions, we observed significant metabolic changes in several metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. In particular, the high-pressure treatment stimulates cell division and triggers the accumulation of UDP-glucose, a critical factor in cell wall formation. This finding highlights the adaptive strategies used by YLB-01 cells to survive in the challenging high-pressure environments of the deep sea. Specifically, we discovered that YLB-01 cells regulate amino acid metabolism, promote carbohydrate metabolism, enhance cell wall synthesis, and improve cell membrane fluidity in response to high pressure. These adaptive mechanisms play essential roles in supporting the survival and growth of YLB-01 in high-pressure conditions. Our study offers valuable insights into the molecular mechanisms underlying the metabolic adaptation of deep-sea microorganisms to high-pressure environments. KEY POINTS: • NMR-based metabolomic and proteomic analyses were conducted on Microbacterium sediminis YLB-01 to investigate the significant alterations in several metabolic pathways in response to high-pressure treatment. • YLB-01 cells used adaptive strategies (such as regulated amino acid metabolism, promoted carbohydrate metabolism, enhanced cell wall synthesis, and improved cell membrane fluidity) to survive in the challenging high-pressure environment of the deep sea. • High-pressure treatment stimulated cell division and triggered the accumulation of UDP-glucose, a critical factor in cell wall formation, in Microbacterium sediminis YLB-01 cells.

Applications of genome-scale metabolic models to investigate microbial metabolic adaptations in response to genetic or environmental perturbations.

Environmental perturbations are encountered by microorganisms regularly and will require metabolic adaptations to ensure an organism can survive in the newly presenting conditions. In order to study the mechanisms of metabolic adaptation in such conditions, various experimental and computational approaches have been used. Genome-scale metabolic models (GEMs) are one of the most powerful approaches to study metabolism, providing a platform to study the systems level adaptations of an organism to different environments which could otherwise be infeasible experimentally. In this review, we are describing the application of GEMs in understanding how microbes reprogram their metabolic system as a result of environmental variation. In particular, we provide the details of metabolic model reconstruction approaches, various algorithms and tools for model simulation, consequences of genetic perturbations, integration of '-omics' datasets for creating context-specific models and their application in studying metabolic adaptation due to the change in environmental conditions.

Cytochrome c regulates hyphal morphogenesis by interfering with cAMP-PKA signaling in Candida albicans.

In the human fungal pathogen Candida albicans, invasive hyphal growth is a well-recognized virulence trait. We employed transposon-mediated genome-wide mutagenesis, revealing that inactivating CTM1 blocks hyphal growth. CTM1 encodes a lysine (K) methyltransferase, which trimethylates cytochrome c (Cyc1) at K79. Mutants lacking CTM1 or expressing cyc1K79A grow as yeast under hyphae-inducing conditions, indicating that unmethylated Cyc1 suppresses hyphal growth. Transcriptomic analyses detected increased levels of the hyphal repressor NRG1 and decreased levels of hyphae-specific genes in ctm1Δ/Δ and cyc1K79A mutants, suggesting cyclic AMP (cAMP)-protein kinase A (PKA) signaling suppression. Co-immunoprecipitation and in vitro kinase assays demonstrated that unmethylated Cyc1 inhibits PKA kinase activity. Surprisingly, hyphae-defective ctm1Δ/Δ and cyc1K79A mutants remain virulent in mice due to accelerated proliferation. Our results unveil a critical role for cytochrome c in maintaining the virulence of C. albicans by orchestrating proliferation, growth mode, and metabolism. Importantly, this study identifies a biological function for lysine methylation on cytochrome c.

Mutagenic effects of a commercial glyphosate-based herbicide formulation on the soil filamentous fungus Aspergillus nidulans depending on the mode of exposure.

Glyphosate-based herbicides (GBH) are the most used pesticides worldwide. This widespread dissemination raises the question of non-target effects on a wide range of organisms, including soil micro-organisms. Despite a large body of scientific studies reporting the harmful effects of GBHs, the health and environmental safety of glyphosate and its commercial formulations remains controversial. In particular, contradictory results have been obtained on the possible genotoxicity of these herbicides depending on the organisms or biological systems tested, the modes and durations of exposure and the sensitivity of the detection technique used. We previously showed that the well-characterized soil filamentous fungus Aspergillus nidulans was highly affected by a commercial GBH formulation containing 450 g/L of glyphosate (R450), even when used at doses far below the agricultural application rate. In the present study, we analysed the possible mutagenicity of R450 in A. nidulans by screening for specific mutants after different modes of exposure to the herbicide. R450 was found to exert a mutagenic effect only after repeated exposure during growth on agar-medium, and depending on the metabolic status of the tested strain. The nature of some mutants and their ability to tolerate the herbicide better than did the wild-type strain suggested that their emergence may reflect an adaptive response of the fungus to offset the herbicide effects. The use of a non-selective molecular approach, the quantitative random amplified polymorphic DNA (RAPD-qPCR), showed that R450 could also exert a mutagenic effect after a one-shot overnight exposure during growth in liquid culture. However, this effect was subtle and no longer detectable when the fungus had previously been repeatedly exposed to the herbicide on a solid medium. This indicated an elevation of the sensitivity threshold of A. nidulans to the R450 mutagenicity, and thus confirmed the adaptive capacity of the fungus to the herbicide.

Isomerization of carotenoids in photosynthesis and metabolic adaptation.

In nature, carotenoids are present as trans- and cis-isomers. Various physical and chemical factors like light, heat, acids, catalytic agents, and photosensitizers can contribute to the isomerization of carotenoids. Living organisms in the process of evolution have developed different mechanisms of adaptation to light stress, which can also involve isomeric forms of carotenoids. Particularly, light stress conditions can enhance isomerization processes. The purpose of this work is to review the recent studies on cis/trans isomerization of carotenoids as well as the role of carotenoid isomers for the light capture, energy transfer, photoprotection in light-harvesting complexes, and reaction centers of the photosynthetic apparatus of plants and other photosynthetic organisms. The review also presents recent studies of carotenoid isomers for the biomedical aspects, showing cis- and trans-isomers differ in bioavailability, antioxidant activity and biological activity, which can be used for therapeutic and prophylactic purposes.

The role of endoplasmic reticulum stress in promoting aerobic glycolysis in cancer cells: An overview.

Aerobic glycolysis, also known as the Warburg effect, is a metabolic phenomenon frequently observed in cancer cells, characterized by the preferential utilization of glucose through glycolysis, even under normal oxygen conditions. This metabolic shift provides cancer cells with a proliferative advantage and supports their survival and growth. While the Warburg effect has been extensively studied, the underlying mechanisms driving this metabolic adaptation in cancer cells remain incompletely understood. In recent years, emerging evidence has suggested a potential link between endoplasmic reticulum (ER) stress and the promotion of aerobic glycolysis in cancer cells. The ER is a vital organelle involved in protein folding, calcium homeostasis, and lipid synthesis. Various cellular stresses, such as hypoxia, nutrient deprivation, and accumulation of misfolded proteins, can lead to ER stress. In response, cells activate the unfolded protein response (UPR) to restore ER homeostasis. However, prolonged or severe ER stress can activate alternative signaling pathways that modulate cellular metabolism, including the promotion of aerobic glycolysis. This review aims to provide an overview of the current understanding regarding the influence of ER stress on aerobic glycolysis in cancer cells to shed light on the complex interplay between ER stress and metabolic alterations in cancer cells. Understanding the intricate relationship between ER stress and the promotion of aerobic glycolysis in cancer cells may provide valuable insights for developing novel therapeutic strategies targeting metabolic vulnerabilities in cancer.

Adaptation to sorbic acid in low sugar promotes resistance of yeast to the preservative.

The weak acid sorbic acid is a common preservative used in soft drink beverages to control microbial spoilage. Consumers and industry are increasingly transitioning to low-sugar food formulations, but potential impacts of reduced sugar on sorbic acid efficacy are barely characterised. In this study, we report enhanced sorbic acid resistance of yeast in low-glucose conditions. We had anticipated that low glucose would induce respiratory metabolism, which was shown previously to be targeted by sorbic acid. However, a shift from respiratory to fermentative metabolism upon sorbic acid exposure of Saccharomyces cerevisiae was correlated with relative resistance to sorbic acid in low glucose. Fermentation-negative yeast species did not show the low-glucose resistance phenotype. Phenotypes observed for certain yeast deletion strains suggested roles for glucose signalling and repression pathways in the sorbic acid resistance at low glucose. This low-glucose induced sorbic acid resistance was reversed by supplementing yeast cultures with succinic acid, a metabolic intermediate of respiratory metabolism (and a food-safe additive) that promoted respiration. The results indicate that metabolic adaptation of yeast can promote sorbic acid resistance at low glucose, a consideration for the preservation of foodstuffs as both food producers and consumers move towards a reduced sugar landscape.

Regulatory mechanisms of one-carbon metabolism enzymes.

One-carbon metabolism is a central metabolic pathway critical for the biosynthesis of several amino acids, methyl group donors, and nucleotides. The pathway mostly relies on the transfer of a carbon unit from the amino acid serine, through the cofactor folate (in its several forms), and to the ultimate carbon acceptors that include nucleotides and methyl groups used for methylation of proteins, RNA, and DNA. Nucleotides are required for DNA replication, DNA repair, gene expression, and protein translation, through ribosomal RNA. Therefore, the one-carbon metabolism pathway is essential for cell growth and function in all cells, but is specifically important for rapidly proliferating cells. The regulation of one-carbon metabolism is a critical aspect of the normal and pathological function of the pathway, such as in cancer, where hijacking these regulatory mechanisms feeds an increased need for nucleotides. One-carbon metabolism is regulated at several levels: via gene expression, posttranslational modification, subcellular compartmentalization, allosteric inhibition, and feedback regulation. In this review, we aim to inform the readers of relevant one-carbon metabolism regulation mechanisms and to bring forward the need to further study this aspect of one-carbon metabolism. The review aims to integrate two major aspects of cancer metabolism-signaling downstream of nutrient sensing and one-carbon metabolism, because while each of these is critical for the proliferation of cancerous cells, their integration is critical for comprehensive understating of cellular metabolism in transformed cells and can lead to clinically relevant insights.