Interactions between Radiation and One-Carbon Metabolism.

Metabolic reprogramming is a hallmark of cancer. Cancer cells rewire one-carbon metabolism, a central metabolic pathway, to turn nutritional inputs into essential biomolecules required for cancer cell growth and maintenance. Radiation therapy, a common cancer therapy, also interacts and alters one-carbon metabolism. This review discusses the interactions between radiation therapy, one-carbon metabolism and its component metabolic pathways.

Maintaining the Chloroplast Redox Balance through the PGR5-Dependent Pathway and the Trx System Is Required for Light-Dependent Activation of Photosynthetic Reactions.

Light-dependent activation of chloroplast enzymes is required for the rapid induction of photosynthesis after a shift from dark to light. The thioredoxin (Trx) system plays a central role in this process. In chloroplasts, the Trx system consists of two pathways: the ferredoxin (Fd)/Trx pathway and the nicotinamide adenine dinucleotide phosphate (NADPH)-Trx reductase C (NTRC) pathway. In Arabidopsis (Arabidopsis thaliana) mutants defective in either pathway, the photoreduction of thiol enzymes was impaired, resulting in decreased carbon fixation. The close relationship between the Fd/Trx pathway and proton gradient regulation 5 (PGR5)-dependent photosystem I cyclic electron transport (PSI CET) in the induction of photosynthesis was recently elucidated. However, how the PGR5-dependent pathway is involved in the NTRC pathway is unclear, although NTRC has been suggested to physically interact with PGR5. In this study, we analyzed Arabidopsis mutants lacking either the PGR5 or the chloroplast NADH dehydrogenase-like complex (NDH)-dependent PSI CET pathway in the ntrc mutant background. The ntrc pgr5 double mutant suppressed both the growth defects and the high non-photochemical quenching phenotype of the ntrc mutant when grown under long-day conditions. By contrast, the inactivation of NDH activity with the chlororespiratory reduction 2-2 mutant failed to suppress either phenotype. We discovered that the phenotypic rescue of ntrc by pgr5 is caused by the partial restoration of Trx-dependent reduction of thiol enzymes. These results suggest that electron partitioning to the PGR5-dependent pathway and the Trx system needs to be properly regulated for the activation of the Calvin-Benson-Bassham cycle enzymes during the induction of photosynthesis.

Light Induced Regulation Pathway of Anthocyanin Biosynthesis in Plants.

Anthocyanins are natural pigments with antioxidant effects that exist in various fruits and vegetables. The accumulation of anthocyanins is induced by environmental signals and regulated by transcription factors in plants. Numerous evidence has indicated that among the environmental factors, light is one of the most signal regulatory factors involved in the anthocyanin biosynthesis pathway. However, the signal transduction of light and molecular regulation of anthocyanin synthesis remains to be explored. Here, we focus on the research progress of signal transduction factors for positive and negative regulation in light-dependent and light-independent anthocyanin biosynthesis. In particular, we will discuss light-induced regulatory pathways and related specific regulators of anthocyanin biosynthesis in plants. In addition, an integrated regulatory network of anthocyanin biosynthesis controlled by transcription factors is discussed based on the significant progress.

Vitamin D and Rheumatic Diseases: A Review of Clinical Evidence.

Vitamin D plays an important role in maintaining a healthy mineralized skeleton. It is also considered an immunomodulatory agent that regulates innate and adaptive immune systems. The aim of this narrative review is to provide general concepts of vitamin D for the skeletal and immune health, and to summarize the mechanistic, epidemiological, and clinical evidence on the relationship between vitamin D and rheumatic diseases. Multiple observational studies have demonstrated the association between a low level of serum 25-hydroxyvitamin D [25(OH)D] and the presence and severity of several rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), spondyloarthropathies, and osteoarthritis (OA). Nevertheless, the specific benefits of vitamin D supplements for the treatment and prevention of rheumatic diseases are less accepted as the results from randomized clinical trials are inconsistent, although some conceivable benefits of vitamin D for the improvement of disease activity of RA, SLE, and OA have been demonstrated in meta-analyses. It is also possible that some individuals might benefit from vitamin D differently than others, as inter-individual difference in responsiveness to vitamin D supplementation has been observed in genomic studies. Although the optimal level of serum 25(OH)D is still debatable, it is advisable it is advisable that patients with rheumatic diseases should maintain a serum 25(OH)D level of at least 30 ng/mL (75 nmol/L) to prevent osteomalacia, secondary osteoporosis, and fracture, and possibly 40-60 ng/mL (100-150 nmol/L) to achieve maximal benefit from vitamin D for immune health and overall health.

Sun Exposure and Vitamin D.

Vitamin D is generally accepted in its importance on the regulation of calcium homeostasis and bone metabolism. Moreover, further health effects due to vitamin D are under discussion. In its effect, vitamin D is more like a hormone. In the classic view, a vitamin is an essential nutrient, which cannot be synthesized independently in the body. Besides nutrition, vitamin D will be produced in the body itself. The skin contains the provitamin D3 7-dehydrocholesterol, a precursor of vitamin D. Provitamin D3 will be photoconverted to previtamin D3 by UVB radiation that penetrates the skin superficially. In this way, the vitamin D metabolism will be started independent of the nutrition. In everyday life, this photosynthesis will be carried out due to the solar UVB radiation penetrating the uncovered skin. In the same spectral waveband range of UVB radiation, which causes the beneficial health effect of starting the vitamin D metabolism, the UVB radiation causes simultaneously acute and chronic harmful health effects as UV erythema (sunburn), skin aging and skin cancer. There is no vitamin D production in the skin without simultaneous DNA damage in the skin. Against this background, risks and benefits have to be balanced carefully.

Risks and Benefits of UV Radiation.

While UV radiation is a skin carcinogen, this should not obscure the growing evidence that sunlight has significant health benefits, including impacts on cardiovascular and metabolic health. Epidemiological and mechanistic evidences for the importance of different wavelengths of sunlight, including blue light and UV radiation, are presented.

Neo-CheckRay: radiation therapy and adenosine pathway blockade to increase benefit of immuno-chemotherapy in early stage luminal B breast cancer, a randomized phase II trial.

BACKGROUND: Residual breast cancer after neo-adjuvant chemotherapy (NACT) predicts disease outcome and is a surrogate for survival in aggressive breast cancer (BC) subtypes. Pathological complete response (pCR) rate, however, is lower for luminal B BC in comparison to the triple negative (TNBC) and HER2+ subtypes. The addition of immune checkpoint blockade (ICB) to NACT has the potential to increase pCR rate but is hampered by the lower immunogenicity of luminal B BC. Novel strategies are needed to stimulate the immune response and increase the response rate to ICB in luminal B BC. METHODS: The Neo-CheckRay trial is a randomized phase II trial investigating the impact of stereotactic body radiation therapy (SBRT) to the primary breast tumor in combination with an anti-CD73 (oleclumab) to increase response to anti PD-L1 (durvalumab) and NACT. The trial is designed as a three-arm study: NACT + SBRT +/- durvalumab +/- oleclumab. The result at surgery will be evaluated using the residual cancer burden (RCB) index as the primary endpoint. Six patients will be included in a safety run-in, followed by a randomized phase II trial that will include 136 evaluable patients in 3 arms. Inclusion is limited to luminal B breast cancers that are MammaPrint genomic high risk. DISCUSSION: combination of ICB with chemotherapy in luminal B BC might benefit from immune priming agents to increase the response rate. As none have been identified so far, this phase II trial will evaluate SBRT and oleclumab as potential immune priming candidates. TRIAL REGISTRATION: trial registered on ClinicalTrials.gov ( NCT03875573 ) on March 14th, 2019.

Metabolic reprograming of antioxidant defense: a precision medicine perspective for radiotherapy of lung cancer?

Radiotherapy plays a key role in the management of lung cancer patients in curative and palliative settings. Traditionally, radiotherapy was either given alone or in combination with surgery, classical cytotoxic chemotherapy, or both. Technical and physical innovations achieved during the last two decades have helped to enhance the accuracy of radiotherapy dose delivery and have facilitated geometric radiotherapy individualization. Furthermore, multimodal combinations with molecularly tailored drugs or immunotherapy yielded promising survival benefits in selected patients. Yet high locoregional failure rates and frequent development of metastases still limit the patient outcome. One major obstacle to successful treatment is the high molecular heterogeneity observed in lung cancer. So far, clinical radiotherapy does not routinely use the knowledge on molecular subtypes with regard to therapy individualization and predictive biomarkers are missing. Herein, altered cancer metabolism has attracted novel attention during recent years as it promotes tumor growth and progression as well as resistance to anticancer therapies. The present perspective will exemplarily highlight how clinically relevant molecular subtypes defined by co-occurring somatic mutations in KRAS-driven lung cancer impact the metabolic phenotype of cancer cells, how the metabolic phenotype supports intrinsic radioresistance by the improved antioxidant defense, and also discuss potential subtype-specific actionable metabolic vulnerabilities. Understanding metabolic phenotypes of radioresistance and metabolic bottlenecks of cancer cells undergoing radiotherapy in a cancer-specific context will offer largely unexploited future avenues for biological individualization and optimization of radiotherapy. Transcriptional profiles will provide additional benefit in defining metabolic phenotypes associated with radioresistance, particularly in cases, where such dependencies cannot be identified by specific somatic mutations.

Radiation-Induced Senescence Reprograms Secretory and Metabolic Pathways in Colon Cancer HCT-116 Cells.

Understanding the global metabolic changes during the senescence of tumor cells can have implications for developing effective anti-cancer treatment strategies. Ionizing radiation (IR) was used to induce senescence in a human colon cancer cell line HCT-116 to examine secretome and metabolome profiles. Control proliferating and senescent cancer cells (SCC) exhibited distinct morphological differences and expression of senescent markers. Enhanced secretion of pro-inflammatory chemokines and IL-1, anti-inflammatory IL-27, and TGF-ß1 was observed in SCC. Significantly reduced levels of VEGF-A indicated anti-angiogenic activities of SCC. Elevated levels of tissue inhibitors of matrix metalloproteinases from SCC support the maintenance of the extracellular matrix. Adenylate and guanylate energy charge levels and redox components NAD and NADP and glutathione were maintained at near optimal levels indicating the viability of SCC. Significant accumulation of pyruvate, lactate, and suppression of the TCA cycle in SCC indicated aerobic glycolysis as the predominant energy source for SCC. Levels of several key amino acids decreased significantly, suggesting augmented utilization for protein synthesis and for use as intermediates for energy metabolism in SCC. These observations may provide a better understanding of cellular senescence basic mechanisms in tumor tissues and provide opportunities to improve cancer treatment.

Novel Transcriptome Study and Detection of Metabolic Variations in UV-B-Treated Date Palm (Phoenix dactylifera cv. Khalas).

Date palm (Phoenix dactylifera) is one of the most widespread fruit crop species and can tolerate drastic environmental conditions that may not be suitable for other fruit species. Excess UV-B stress is one of the greatest concerns for date palm trees and can cause genotoxic effects. Date palm responds to UV-B irradiation through increased DEG expression levels and elaborates upon regulatory metabolic mechanisms that assist the plants in adjusting to this exertion. Sixty-day-old Khalas date palm seedlings (first true-leaf stage) were treated with UV-B (wavelength, 253.7 nm; intensity, 75 µW cm-2 for 72 h (16 h of UV light and 8 h of darkness). Transcriptome analysis revealed 10,249 and 12,426 genes whose expressions were upregulated and downregulated, respectively, compared to the genes in the control. Furthermore, the differentially expressed genes included transcription factor-encoding genes and chloroplast- and photosystem-related genes. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect metabolite variations. Fifty metabolites, including amino acids and flavonoids, showed changes in levels after UV-B excess. Amino acid metabolism was changed by UV-B irradiation, and some amino acids interacted with precursors of different pathways that were used to synthesize secondary metabolites, i.e., flavonoids and phenylpropanoids. The metabolite content response to UV-B irradiation according to hierarchical clustering analysis showed changes in amino acids and flavonoids compared with those of the control. Amino acids might increase the function of scavengers of reactive oxygen species by synthesizing flavonoids that increase in response to UV-B treatment. This study enriches the annotated date palm unigene sequences and enhances the understanding of the mechanisms underlying UV-B stress through genetic manipulation. Moreover, this study provides a sequence resource for genetic, genomic and metabolic studies of date palm.

Optogenetic Amplification Circuits for Light-Induced Metabolic Control.

Dynamic control of microbial metabolism is an effective strategy to improve chemical production in fermentations. While dynamic control is most often implemented using chemical inducers, optogenetics offers an attractive alternative due to the high tunability and reversibility afforded by light. However, a major concern of applying optogenetics in metabolic engineering is the risk of insufficient light penetration at high cell densities, especially in large bioreactors. Here, we present a new series of optogenetic circuits we call OptoAMP, which amplify the transcriptional response to blue light by as much as 23-fold compared to the basal circuit (OptoEXP). These circuits show as much as a 41-fold induction between dark and light conditions, efficient activation at light duty cycles as low as ∼1%, and strong homogeneous light-induction in bioreactors of at least 5 L, with limited illumination at cell densities above 40 OD600. We demonstrate the ability of OptoAMP circuits to control engineered metabolic pathways in novel three-phase fermentations using different light schedules to control enzyme expression and improve production of lactic acid, isobutanol, and naringenin. These circuits expand the applicability of optogenetics to metabolic engineering.

Effects of Different Short-Term UV-B Radiation Intensities on Metabolic Characteristics of Porphyra haitanensis.

The effects of ultraviolet (UV) radiation, particularly UV-B on algae, have become an important issue as human-caused depletion of the protecting ozone layer has been reported. In this study, the effects of different short-term UV-B radiation on the growth, physiology, and metabolism of Porphyra haitanensis were examined. The growth of P. haitanensis decreased, and the bleaching phenomenon occurred in the thalli. The contents of total amino acids, soluble sugar, total protein, and mycosporine-like amino acids (MAAs) increased under different UV-B radiation intensities. The metabolic profiles of P. haitanensis differed between the control and UV-B radiation-treated groups. Most of the differential metabolites in P. haitanensis were significantly upregulated under UV-B exposure. Short-term enhanced UV-B irradiation significantly affected amino acid metabolism, carbohydrate metabolism, glutathione metabolism, and phenylpropane biosynthesis. The contents of phenylalanine, tyrosine, threonine, and serine were increased, suggesting that amino acid metabolism can promote the synthesis of UV-absorbing substances (such as phenols and MAAs) by providing precursor substances. The contents of sucrose, D-glucose-6-phosphate, and beta-D-fructose-6-phosphate were increased, suggesting that carbohydrate metabolism contributes to maintain energy supply for metabolic activity in response to UV-B exposure. Meanwhile, dehydroascorbic acid (DHA) was also significantly upregulated, denoting effective activation of the antioxidant system. To some extent, these results provide metabolic insights into the adaptive response mechanism of P. haitanensis to short-term enhanced UV-B radiation.

Dynamical Modeling of Optogenetic Circuits in Yeast for Metabolic Engineering Applications.

Dynamic control of engineered microbes using light via optogenetics has been demonstrated as an effective strategy for improving the yield of biofuels, chemicals, and other products. An advantage of using light to manipulate microbial metabolism is the relative simplicity of interfacing biological and computer systems, thereby enabling in silico control of the microbe. Using this strategy for control and optimization of product yield requires an understanding of how the microbe responds in real-time to the light inputs. Toward this end, we present mechanistic models of a set of yeast optogenetic circuits. We show how these models can predict short- and long-time response to varying light inputs and how they are amenable to use with model predictive control (the industry standard among advanced control algorithms). These models reveal dynamics characterized by time-scale separation of different circuit components that affect the steady and transient levels of the protein under control of the circuit. Ultimately, this work will help enable real-time control and optimization tools for improving yield and consistency in the production of biofuels and chemicals using microbial fermentations.

Differences in the Formation Mechanism of Giant Colonies in Two Phaeocystis globosa Strains.

Phaeocystis globosa has become one of the primary causes of harmful algal bloom in coastal areas of southern China in recent years, and it poses a serious threat to the marine environment and other activities depending upon on it (e.g., aquaculture, cooling system of power plants), especially in the Beibu Gulf. We found colonies of P. globosa collected form Guangxi (China) were much larger than those obtained from Shantou cultured in lab. To better understand the causes of giant colonies formation, colonial cells collected from P. globosa GX strain (GX-C) and ST strain (ST-C) were separated by filtration. Morphological observations, phylogenetic analyses, rapid light-response curves, fatty acid profiling and transcriptome analyses of two type cells were performed in the laboratory. Although no differences in morphology and 18S rRNA sequences of these cells were observed, the colonies of GX strain (4.7 mm) are 30 times larger than those produced by the ST strain (300 µm). The rapid light-response curve of GX-C was greater than that of ST-C, consistent with the upregulated photosynthetic system, while the fatty acid content of GX-C was lower than that of ST-C, also consistent with the downregulated synthesis of fatty acids and the upregulated degradation of fatty acids. In summary, the increased energy generated by GX-C is allocated to promote the secretion of extracellular polysaccharides for colony formation. We performed a physiological and molecular assessment of the differences between the GX-C and ST-C strains, providing insights into the mechanisms of giant colonies formation in P. globosa.

Parthenium hysterophorus steps up Ca-regulatory pathway in defence against highlight intensities.

Parthenium hysterophorus exhibits tolerance to a great extent against abiotic stresses including high light intensities. In this study, P. hysterophorus was subjected to three different light intensities viz. control (CL, 250 µmol photons m-2 s-1), moderately high (ML, 500 µmol photons m-2 s-1) and high (HL, 1000 µmol photons m-2 s-1) for assessment of biochemical and physiological responses at 3 and 5 days after treatment (DAT). Proteomic responses were also observed at 5 DAT. Level of oxidative stress marker, abundance of H2O2 and O2- was highest in leaves exposed to HL followed by ML treatment. Biomass accumulation, photosynthetic parameters, chloroplast and mitochondrial integrity were also affected by both ML and HL treatments. Differential protein expression data showed modulation of thirty-eight proteins in ML and HL intensities. P. hysterophorus exhibited good ability to survive in ML then HL treatment as demonstrated by enhancement of the antioxidant system and photosynthesis. Furthermore, P. hysterophorus mobilized some key proteins related to calcium signaling, which in turn coordinate physiological homeostasis under stress. Proline and total soluble sugar content were high under stress; however, results of simulated experiment of our study indicate such accumulation of osmolytes may inhibit photon-availability to chloroplast. These results clarify our understanding of the mechanisms underlying the light stress tolerance of P. hysterophorus.

Multi-omics analysis on an agroecosystem reveals the significant role of organic nitrogen to increase agricultural crop yield.

Both inorganic fertilizer inputs and crop yields have increased globally, with the concurrent increase in the pollution of water bodies due to nitrogen leaching from soils. Designing agroecosystems that are environmentally friendly is urgently required. Since agroecosystems are highly complex and consist of entangled webs of interactions between plants, microbes, and soils, identifying critical components in crop production remain elusive. To understand the network structure in agroecosystems engineered by several farming methods, including environmentally friendly soil solarization, we utilized a multiomics approach on a field planted with Brassica rapa We found that the soil solarization increased plant shoot biomass irrespective of the type of fertilizer applied. Our multiomics and integrated informatics revealed complex interactions in the agroecosystem showing multiple network modules represented by plant traits heterogeneously associated with soil metabolites, minerals, and microbes. Unexpectedly, we identified soil organic nitrogen induced by soil solarization as one of the key components to increase crop yield. A germ-free plant in vitro assay and a pot experiment using arable soils confirmed that specific organic nitrogen, namely alanine and choline, directly increased plant biomass by acting as a nitrogen source and a biologically active compound. Thus, our study provides evidence at the agroecosystem level that organic nitrogen plays a key role in plant growth.

Mimicking of Phase I Metabolism Reactions of Molindone by HLM and Photocatalytic Methods with the Use of UHPLC-MS/MS.

Establishing the metabolism pathway of the drug undergoing the hepatic biotransformation pathway is one of the most important aspects in the preclinical discovery process since the presence of toxic or reactive metabolites may result in drug withdrawal from the market. In this study, we present the structural elucidation of six, not described yet, metabolites of an antipsychotic molecule: molindone. The elucidation of metabolites was supported with a novel photocatalytical approach with the use of WO3 and WS2 assisted photochemical reactions. An UHPLC-ESI-Q-TOF combined system was used for the registration of all obtained metabolite profiles as well as to record the high resolution fragmentation spectra of the observed transformation products. As a reference in the in vitro metabolism simulation method, the incubation with human liver microsomes was used. Chemometric comparison of the obtained profiles pointed out the use of the WO3 approach as being more convenient in the field of drug metabolism studies. Moreover, the photocatalysis was used in the direction of the main drug metabolite synthesis in order to further isolation and characterization.

Altered levels of AOX1a expression result in changes in metabolic pathways in Arabidopsis thaliana plants acclimated to low dose rates of ultraviolet B radiation.

UV-B is a damaging component of solar radiation that inevitably reaches the Earth's surface. Plants have developed response mechanisms to adapt to UVB exposure. The alternative oxidase (AOX) catalyzes the ATP-uncoupling cyanide-resistant alternative pathway (AP) in plant mitochondria and is thought to be an important part of the cellular defense network under stress conditions. This study aimed to unravel the poorly understood functional significance of AOX1a induction in Arabidopsis thaliana leaves exposed to ecologically relevant doses of UVB radiation, by comparing wild-type (WT) plants with plants with modified expression of the AOX1a gene, either downregulated by antisense (AS-12) or overexpressed (XX-2). UVB exposure resulted in a phenotypic difference between lines. AOX1a overexpression resulted in the highest induction of AOX1A synthesis and MnSOD activity, and the lowest ROS level without pronounced changes in the phenotype relative to other genotypes. In AS-12 plants, expression of the majority of the genes encoding AOX was detected, other non-phosphorylating pathway components and antioxidant enzymes increased along with anthocyanin accumulation in leaves, and the ROS content was lower than in the WT. In addition to the expected AOX1 protein size (34 kDa), an AOX1 30 kDa band appeared under UVB exposure in all genotypes. However, in AS-12, the alterations in the transcript level and in the abundance of AOX1 protein isoforms induced by UVB could not fully functionally compensate for the lack of AOX1A. This was confirmed by the observed low AP capacity and increased levels of the oxidized form of ascorbate. These results highlight the importance of AOX in plant response to UVB for the control of a balanced metabolism, and indicate that AOX1a plays a key role in the regulation of the stress response.

Metabolomics of red-light-induced stomatal opening in Arabidopsis thaliana: Coupling with abscisic acid and jasmonic acid metabolism.

Environmental stimuli-triggered stomatal movement is a key physiological process that regulates CO2 uptake and water loss in plants. Stomata are defined by pairs of guard cells that perceive and transduce external signals, leading to cellular volume changes and consequent stomatal aperture change. Within the visible light spectrum, red light induces stomatal opening in intact leaves. However, there has been debate regarding the extent to which red-light-induced stomatal opening arises from direct guard cell sensing of red light versus indirect responses as a result of red light influences on mesophyll photosynthesis. Here we identify conditions that result in red-light-stimulated stomatal opening in isolated epidermal peels and enlargement of protoplasts, firmly establishing a direct guard cell response to red light. We then employ metabolomics workflows utilizing gas chromatography mass spectrometry and liquid chromatography mass spectrometry for metabolite profiling and identification of Arabidopsis guard cell metabolic signatures in response to red light in the absence of the mesophyll. We quantified 223 metabolites in Arabidopsis guard cells, with 104 found to be red light responsive. These red-light-modulated metabolites participate in the tricarboxylic acid cycle, carbon balance, phytohormone biosynthesis and redox homeostasis. We next analyzed selected Arabidopsis mutants, and discovered that stomatal opening response to red light is correlated with a decrease in guard cell abscisic acid content and an increase in jasmonic acid content. The red-light-modulated guard cell metabolome reported here provides fundamental information concerning autonomous red light signaling pathways in guard cells.

Plant sulphur metabolism is stimulated by photorespiration.

Intense efforts have been devoted to describe the biochemical pathway of plant sulphur (S) assimilation from sulphate. However, essential information on metabolic regulation of S assimilation is still lacking, such as possible interactions between S assimilation, photosynthesis and photorespiration. In particular, does S assimilation scale with photosynthesis thus ensuring sufficient S provision for amino acids synthesis? This lack of knowledge is problematic because optimization of photosynthesis is a common target of crop breeding and furthermore, photosynthesis is stimulated by the inexorable increase in atmospheric CO2. Here, we used high-resolution 33S and 13C tracing technology with NMR and LC-MS to access direct measurement of metabolic fluxes in S assimilation, when photosynthesis and photorespiration are varied via the gaseous composition of the atmosphere (CO2, O2). We show that S assimilation is stimulated by photorespiratory metabolism and therefore, large photosynthetic fluxes appear to be detrimental to plant cell sulphur nutrition.