Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Fish mucus has important biological and ecologicalroles such as defense against fish pathogens andchemical mediation among several species. A non-targetedliquid chromatography–mass spectrometry metabolomicapproach was developed to study gill mucus of eight butterflyfishspecies in Moorea (French Polynesia), and theinfluence of several fish traits (geographic site and reefhabitat, species taxonomy, phylogeny, diet and parasitismlevels) on the metabolic variability was investigated. Abiphasic extraction yielding two fractions (polar and apolar)was used. Fish diet (obligate corallivorous, facultativecorallivorous or omnivorous) arose as the main driver ofthe metabolic differences in the gill mucus in both fractions,accounting for 23% of the observed metabolic variabilityin the apolar fraction and 13% in the polar fraction.A partial least squares discriminant analysis allowed us toidentify the metabolites (variable important in projection,VIP) driving the differences between fish with differentdiets (obligate corallivores, facultative corallivores andomnivorous). Using accurate mass data and fragmentationdata, we identified some of these VIP as glycerophosphocholines,ceramides and fatty acids. Level of monogeneangill parasites was the second most important factor shapingthe gill mucus metabolome, and it explained 10% of themetabolic variability in the polar fraction and 5% in theapolar fraction. A multiple regression tree revealed that themetabolic variability due to parasitism in the polar fractionwas mainly due to differences between non-parasitized andparasitized fish. Phylogeny and butterflyfish species werefactors contributing significantly to the metabolic variabilityof the apolar fraction (10 and 3%, respectively) buthad a less pronounced effect in the polar fraction. Finally,geographic site and reef habitat of butterflyfish species didnot influence the gill mucus metabolome of butterflyfishes.
ISSN: 0722-4028

hal-01563312
https://hal-univ-perp.archives-ouvertes.fr/hal-01563312
DOI : 10.1007/s00338-017-1554-0

Éditeur(s) : HAL CCSD
Résumé : The bacterial microbiota of ants (Hymenoptera: Formicidae) is known to have a defensive role in social insects, particularly for leaf-cutting ants (Formicidae: Attini) due to the use of antimicrobial molecules produced by cuticular actinobacteria. In this thesis, we studied the bacterial microbiota of ants in French Guyana using different approaches based on natural products chemistry and molecular ecology. The first chapter describes the isolation, identification, culture and biological evaluations of 43 cuticular actinobacteria. Antagonism bioassays of isolated strains and antibiotic activities of the culture extracts against human pathogens are presented as well as the identification of an antimicrobial cyclic dipeptide (Cyclo (LPro-LPhe)) isolated from a strain close to Streptomyces thioluteus. Moreover, the implementation of molecular networks applied to UPLC/MS/MS analysis of actinobacterial cocultures allowed us to explore the diversity of metabolites produced under these conditions. The second chapter presents a methodological study to evaluate the capacity of four DNA extraction methods, in terms of richness and composition of the cuticular bacterial microbiota, in high-throughput sequencing from Atta cephalotes and Pseudomyrmex penetrator. The results of metabarcoding highlight two methods of extraction and reveal inter- and intraspecific differences in the composition of cuticular bacterial communities. Finally, chapter three describes the composition of the cuticular bacterial microbiota of Camponotus femoratus and Crematogaster levior in ant garden and the results reveal the acquisition in the environment of a part of the microbiota. In parallel, metabolomic analyses of ant’s cuticle show, on the contrary, a greater specificity related to the ant species. Future researches focusing on statistical analysis strategies combining metabarcoding and metabolomics data are discussed.
Le microbiote bactérien cuticulaire des fourmis (Hymenoptera : Formicidae) est connu pour avoir un rôle défensif chez ces insectes sociaux, notamment chez les fourmis attines (Formicidae : Attini) grâce l’utilisation de molécules antimicrobiennes produites par des actinobactéries cuticulaires. Dans le cadre de cette thèse, nous avons étudié le microbiote bactérien des fourmis de Guyane en utilisant différentes approches en chimie des produits naturels et en écologie moléculaire. Le premier chapitre décrit l’isolement, l’identification, la culture et l’évaluation biologique de 43 actinobactéries cuticulaires de fourmis de Guyane. Les tests d’antagonismes des souches isolées et l’activité antibiotique des extraits de culture contre des micro-organismes pathogènes humains sont présentés ainsi que l’identification d’un dipeptide cyclique (Cyclo(LPro-LPhe)) antimicrobien qui a été isolé à partir d’une souche proche de Streptomyces thioluteus. Par ailleurs, la mise en œuvre de réseaux moléculaires appliqués à une analyse par UPLC/MS/MS de cocultures d’actinobactéries a permis d’explorer la diversité des métabolites produits dans ces conditions. Le deuxième chapitre présente une étude méthodologique pour comparer quatre méthodes d’extraction d’ADN, en termes de richesse et de composition du microbiote bactérien cuticulaire, par séquençage haut débit à partir des espèces Atta cephalotes et Pseudomyrmex penetrator. Les résultats du métabarcoding ADN mettent en lumière deux méthodes d’extraction et révèlent des différences inter- et intraspécifiques dans la composition des communautés bactériennes cuticulaires. Enfin, le chapitre trois décrit la composition du microbiote bactérien cuticulaire des espèces Camponotus femoratus et Crematogaster levior dans les jardins de fourmis. Les résultats soulignent l’acquisition d’une partie du microbiote dans l’environnement. En parallèle l’analyse métabolomique des cuticules montre à contrario une plus grande spécificité liée à l’espèce de fourmi. Les recherches futures axées sur les stratégies d’analyses statistiques combinant le métabarcoding et la métabolomique sont discutées.
https://tel.archives-ouvertes.fr/tel-01537793

NNT : 2017YANE0003
tel-01537793
https://tel.archives-ouvertes.fr/tel-01537793
https://tel.archives-ouvertes.fr/tel-01537793/document
https://tel.archives-ouvertes.fr/tel-01537793/file/thesecarolinebirer.pdf

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
Humans may be exposed via their environment to multiple chemicals as a consequence of human activities and use of synthetic products. Little knowledge is routinely generated on the hazards of these chemical mixtures. The metabolomic approach is widely used to identify metabolic pathways modified by diseases, drugs, or exposures to toxicants. This review, based on the state of the art of the current applications of metabolomics in environmental health, attempts to determine whether metabolomics might constitute an original approach to the study of associations between multiple, low-dose environmental exposures in humans. Studying the biochemical consequences of complex environmental exposures is a challenge demanding the development of careful experimental and epidemiological designs, in order to take into account possible confounders associated with the high level of interindividual variability induced by different lifestyles. The choices of populations studied, sampling and storage procedures, statistical tools used, and system biology need to be considered. Suggestions for improved experimental and epidemiological designs are described. Evidence indicates that metabolomics may be a powerful tool in environmental health in the identification of both complex exposure biomarkers directly in human populations and modified metabolic pathways, in an attempt to improve understanding the underlying environmental causes of diseases. Nevertheless, the validity of biomarkers and relevancy of animal-to-human extrapolation remain key challenges that need to be properly explored.
ISSN: 1093-7404

hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00976116/file/Potential_input_from_metabolomics_accepted.pdf
DOI : 10.1080/10937404.2013.860318

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: The use of pesticides and the related environmental contaminations can lead to human exposure to various molecules. In early-life, such exposures could be responsible for adverse developmental effects. However, human health risks associated with exposure to complex mixtures are currently under-explored. OBJECTIVE: THIS PROJECT AIMS AT ANSWERING THE FOLLOWING QUESTIONS: What is the influence of exposures to multiple pesticides on the metabolome? What mechanistic pathways could be involved in the metabolic changes observed? METHODS: Based on the PELAGIE cohort (Brittany, France), 83 pregnant women who provided a urine sample in early pregnancy, were classified in 3 groups according to the surface of land dedicated to agricultural cereal activities in their town of residence. Nuclear magnetic resonance-based metabolomics analyses were performed on urine samples. Partial Least Squares Regression-Discriminant Analysis (PLS-DA) and polytomous regressions were used to separate the urinary metabolic profiles from the 3 exposure groups after adjusting for potential confounders. RESULTS: The 3 groups of exposure were correctly separated with a PLS-DA model after implementing an orthogonal signal correction with pareto standardizations (R2 = 90.7% and Q2 = 0.53). After adjusting for maternal age, parity, body mass index and smoking habits, the most statistically significant changes were observed for glycine, threonine, lactate and glycerophosphocholine (upward trend), and for citrate (downward trend). CONCLUSION: This work suggests that an exposure to complex pesticide mixtures induces modifications of metabolic fingerprints. It can be hypothesized from identified discriminating metabolites that the pesticide mixtures could increase oxidative stress and disturb energy metabolism.
ISSN: 1932-6203

inserm-00863407
http://www.hal.inserm.fr/inserm-00863407
http://www.hal.inserm.fr/inserm-00863407/document
http://www.hal.inserm.fr/inserm-00863407/file/journal.pone.0064433.pdf
PUBMED : 23704985

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Because earthworms sustain soil functioning and fertility, there is a need to advance the knowledge of their adaptation potential to chemicals in anthropogenic landscapes. Our hypothesis is that there is acclimation to organic chemicals (pesticides) in earthworms that durably persist under conventional farming in anthropogenic landscapes. The adaptation capability of two populations of earthworms (Aporectodea caliginosa) having a different chemical exposure history, - one originating from 20 years of organic farming (naïve population) and another from 20 years of conventional farming (pre-exposed population) - to cope with soil organic pollutant (Opus®, epoxiconazole a worldwide used fungicide) were investigated. Several complementary metabolic and energetic endpoints were followed, and cast production was assessed as a behavioural biomarker related to earthworms ecological role for the soil. Basal metabolism reflected by respiration rate was increased in both fungicide-exposed worms compared to controls. Glycogen resources were decreased in the same proportion in the two populations but more rapidly for the naïve (7 days) than for the pre-exposed population (28 days). Soluble protein and most amino-acids contents increased in the pre-exposed population only, suggesting a detoxification mechanism. Metabolomic profiles showed a cut-off between fungicide-exposed and control groups in the pre-exposed earthworms only, with an increase in most of the metabolites. Exposure to a low dose of epoxiconazole increased cast production of pre-exposed earthworms, and this resulted in an increase in pesticide disappearance. As far as we know, this is the first study which evidenced there is an acclimation to an agricultural chemical in earthworms derived from conventional farming that also relates to a change in their burrowing behaviour, and for which larger consequences for the soil ecosystem need to be addressed. This original finding is of major interest in the frame of ecosystem resilience to global changes. Whether this physiological adaptation is a general pattern of response against fungicides or other pesticides would need to be confirmed with other molecules and agricultural contexts.
Soil Biology and Biochemistry

hal-01005821
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01005821
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01005821/document
DOI : 10.1016/j.soilbio.2014.01.032

Éditeur(s) : GFP : Groupe Français des Pesticides
Extrait de : "Protection des cultures et santé environnementale : héritages et conceptions nouvelles" : congrès, le 26 mai 2014. Université des Antilles et de la Guyane
Description : Les résultats de cette analyse montrent que des approches globales, non ciblées peuvent permettre de discriminer des groupes d'individus exposés à des mélanges complexes de pesticides à faibles doses. Les modifications subtiles du métabolome, si elles ne peuvent être considérées, a priori, comme des effets néfastes, indiquent néanmoins que des voies métaboliques peuvent être modifiées par une exposition à des pesticides à faibles doses.
Siècle(s) traité(s) : 21
Droits : CC-BY-NC-ND - Attribution - Pas d'utilisation commerciale - Pas de modification
Permalien : http://www.manioc.org/fichiers/V14219
V14219

Éditeur(s) : HAL CCSD Springer Verlag
Résumé : International audience
Introduction The Latitudinal Gradient Hypothesis (LGH) foresees that specialized metabolites are overexpressed under low latitudes, where organisms are subjected to higher herbivory pressure. The widespread macroalga Asparagopsis taxiformis is composed of six distinct genetic lineages, some of them being introduced in many regions. Objectives To study (i) metabolic fingerprints of the macroalga and (ii) its bioactivity in space and time, both as proxies of its investment in defensive traits, in order to assess links between bioactivities and metabotypes with macroalgal invasiveness. Methods 289 macroalgal individuals, from four tropical and three temperate regions, were analyzed using untargeted metabolomics and the standardized Microtox (R) assay. Results Metabotypes showed a low divergence between tropical and temperate populations, while bioactivities were higher in temperate populations. However, these phenotypes varied significantly in time, with a higher variability in tropical regions. Bioactivities were high and stable in temperate regions, whereas they were low and much variable in tropical regions. Although the introduced lineage two exhibited the highest bioactivities, this lineage could also present variable proliferation fates. Conclusion The metabolomic approach partly discriminates macroalgal populations from various geographic origins. The production of chemical defenses assessed by the bioactivity assay does not match the macroalgal genetic lineage and seems more driven by the environment. The higher content of chemical defenses in temperate versus tropical populations is not in accordance with the LGH and cannot be related to the invasiveness of the macroalgae.
ISSN: 1573-3882

hal-01681538
https://hal.archives-ouvertes.fr/hal-01681538
DOI : 10.1007/s11306-017-1169-z

Éditeur(s) : HAL CCSD
Résumé : International audience
High-mass-resolution imaging mass spectrometry promises to localize hundreds of metabolites in tissues, cell cultures, and agar plates with cellular resolution, but it is hampered by the lack of bioinformatics tools for automated metabolite identification. We report pySM, a framework for false discovery rate (FDR)-controlled metabolite annotation at the level of the molecular sum formula, for high-mass-resolution imaging mass spectrometry (https://github.com/alexandrovteam/pySM). We introduce a metabolite-signal match score and a target-decoy FDR estimate for spatial metabolomics. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Nature Methods

hal-01467553
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01467553
DOI : 10.1038/nmeth.4072
PUBMED : 27842059

Éditeur(s) : HAL CCSD
Résumé : The aim of this work was to search for new bioactive compounds, displaying either antiplasmodial or antifungal activity. Two strategies were developed here: the evaluation of traditional remedies identified as antimalarial through ethnopharmacological study, and the search for antifungal essential oils, the criterium being here a bioinspired approach. Our work led to the discovery that the antimalarial activity of Quassia amara L. (Simaroubaceae) fresh young leaves was due to the presence of a known quassinoid, simalikalactone D. In the case of Psidium acutangulum DC. (Myrtaceae), a flavonol glycosides mixture explained the activity observed for the decoction. The search for antifungal essential oils from the Amazonian flora lead to the identification of several interesting species, thus validating our bioinspired strategy. The essential oil of Otacanthus azureus (Linden) Ronse was among the most active ones, either alone or in combination with azole drugs. Eventually, a metabolomic study of the GC/MS composition of these oils allowed us to develop a statistical tool which could help to select interesting antifungal products. This work thus demonstrate the major interest of the two strategies - ethnopharmacology and bioinspiration - for the search of new bioactive compounds.
L'objectif du travail effectué était la recherche de nouvelles substances actives d'origine végétale, présentant soit une activité antiplasmodiale soit une activité antifongique. Cette étude a été menée suivant deux stratégies différentes: l'étude de remèdes traditionnels antipaludiques identifiés suite à des enquêtes ethnopharmacologiques, et la mise en évidence des propriétés antifongiques d'huiles essentielles grâce à une stratégie bioinspirée. La première partie du travail a permis de mettre en évidence le rôle d'un quassinoïde connu, la simalikalactone D, dans l'activité antipaludique d'une tisane de jeunes feuilles fraîches de Quassia amara L. (Simaroubaceae). Dans le cas de la décoction de rameaux de Psidium acutangulum DC. (Myrtaceae), c'est cette fois un mélange de flavonoïdes glycosylés qui est responsable de l'activité du remède. Dans le cadre de la recherche de nouvelles substances antifongiques, le criblage effectué a permis d'identifier de nombreuses huiles essentielles présentant des activités intéressantes, validant ainsi la démarche bioinspirée retenue dans ce cas. L'huile essentielle d'Otacanthus azureus (Linden) Ronse a en particulier démontré une activité remarquable, à la fois seule et en combinaison avec des antifongiques azolés. Enfin, l'étude métabolomique de la composition des huiles essentielles a permis de mettre au point un outil pouvant orienter la sélection des huiles en fonction des données obtenues en GC/MS dans l'optique de la recherche de nouvelles substances antifongiques. Ce travail démontre donc la validité des stratégies retenues - ethnopharmacologie et bioinspiration - dans la recherche de nouvelles substances bioactives.
https://tel.archives-ouvertes.fr/tel-00718910

tel-00718910
https://tel.archives-ouvertes.fr/tel-00718910
https://tel.archives-ouvertes.fr/tel-00718910/document
https://tel.archives-ouvertes.fr/tel-00718910/file/TheseEH2011_SUBST_BIOACTIVES.pdf

Éditeur(s) : HAL CCSD
Résumé : The ecological success of cnidarian-dinoflagellate symbiosis mainly relies on nutrient recycling. Environmental changes, such as global warming or pollution, often result to symbiosis breakdown, also called cnidarian bleaching. The understanding of mechanisms regulating the symbiosis establishment, maintenance and breakdown is essential to prevent massive bleaching phenomena. In this respect, my PhD project focused on the characterization of chemical mediators expressed in the sea anemone Anemonia viridis, their localization and their modulation by stress conditions. A comparative study was first conducted to characterize the chemical mediators and analyze their distribution within the symbiotic sea anemone. We described a great abundance and diversity of lipids in A. viridis tissues. From these results, we proposed possible transfers of FAs between the symbiotic partners. A thermal stress and a chemical stress have also been applied in laboratory-controlled conditions in order to induce symbiosis breakdown and bleaching of the sea anemones, in order to correlate A. viridis metabolome to its symbiotic status. A mapping of these metabolites has been performed by MALDI-MSI of tentacle cross-sections, as well as their evolution following stress. Some betaine lipids have thus been proposed as short-term indicators of stress. A. viridis stress response has also been evaluated with a lipidomic approach, and allowed to identify 3 lipid indicators of early stress response based on membrane fluidity markers. Overall, this study provides insight on key chemical mediators that may regulate the symbiosis maintenance, and may contribute to the symbiosis breakdown.
Le succès évolutif des Cnidaires symbiotiques réside en grande partie dans leurs échanges trophiques établis avec les Dinoflagellés du genre Symbiodinium. Cependant, le réchauffement climatique global ainsi que les pollutions ont un impact fort sur les écosystèmes coralliens, notamment en conduisant à la rupture de la symbiose, phénomène appelé blanchissement. La compréhension des mécanismes qui régissent l’établissement, le maintien et la rupture de la symbiose est essentielle à la prévention des épisodes de blanchissement massif. Dans ce contexte, les objectifs de mon projet de thèse sont de caractériser les médiateurs chimiques de l’anémone de mer Anemonia viridis, de les localiser, et d’analyser leur réponse face à un stress. Parmi les composés caractérisés, les lipides et les bétaïnes sont les plus abondants et présentent une grande diversité. Certains sont transférés des symbiotes vers l’hôte. Des anémones de mer ont ensuite été traitées en laboratoire afin de provoquer la rupture de la symbiose et le blanchissement des individus. Une étude cinétique a été menée par une approche globale comparative identique à celle réalisée sur l’anémone symbiotique. Par ailleurs, une cartographie de l’évolution de composés clé a été réalisée par MALDI-MSI. La réponse au stress a été évaluée et a permis d’identifier des lipides de bétaïne et trois indicateurs lipidiques comme marqueurs de réponse précoce au stress. L’ensemble de ces résultats apporte de nouveaux éléments de réponse concernant le rôle des médiateurs chimiques clés dans le maintien de la symbiose, ainsi que leur influence sur sa rupture.
https://tel.archives-ouvertes.fr/tel-01310668

NNT : 2015NICE4108
tel-01310668
https://tel.archives-ouvertes.fr/tel-01310668
https://tel.archives-ouvertes.fr/tel-01310668/document
https://tel.archives-ouvertes.fr/tel-01310668/file/2015NICE4108.pdf

Résumé : L’objectif du travail effectué était la recherche de nouvelles substances actives d’origine végétale, présentant soit une activité antiplasmodiale soit une activité antifongique. Cette étude a été menée suivant deux stratégies différentes: l’étude de remèdes traditionnels antipaludiques identifiés suite à des enquêtes ethnopharmacologiques, et la mise en évidence des propriétés antifongiques d’huiles essentielles grâce à une stratégie bioinspirée. La première partie du travail a permis de mettre en évidence le rôle d’un quassinoïde connu, la simalikalactone D, dans l’activité antipaludique d’une tisane de jeunes feuilles fraîches de Quassia amara L. (Simaroubaceae). Dans le cas de la décoction de rameaux de Psidium acutangulum DC. (Myrtaceae), c’est cette fois un mélange de flavonoïdes glycosylés qui est responsable de l’activité du remède. Dans le cadre de la recherche de nouvelles substances antifongiques, le criblage effectué a permis d’identifier de nombreuses huiles essentielles présentant des activités intéressantes, validant ainsi la démarche bioinspirée retenue dans ce cas. L’huile essentielle d’Otacanthus azureus (Linden) Ronse a en particulier démontré une activité remarquable, à la fois seule et en combinaison avec des antifongiques azolés. Enfin, l’étude métabolomique de la composition des huiles essentielles a permis de mettre au point un outil pouvant orienter la sélection des huiles en fonction des données obtenues en GC/MS dans l’optique de la recherche de nouvelles substances antifongiques. Ce travail démontre donc la validité des stratégies retenues – ethnopharmacologie et bioinspiration – dans la recherche de nouvelles substances bioactives.
The aim of this work was to search for new bioactive compounds, displaying either antiplasmodial or antifungal activity. Two strategies were developed here: the evaluation of traditional remedies identified as antimalarial through ethnopharmacological studies, and the search for antifungal essential oils, the criterium being here a bioinspired approach. Our work led to the discovery that the antimalarial activity of Quassia amara L. (Simaroubaceae) fresh young leaves was due to the presence of a known quassinoid, simalikalactone D. In the case of Psidium acutangulum DC. (Myrtaceae), a flavonol glycosides mixture explained the activity observed for the decoction. The search for antifungal essential oils from the Amazonian flora led to the identification of several interesting species, thus validating our bioinspired strategy. The essential oil of Otacanthus azureus (Linden) Ronse was among the most active ones, either alone or in combination with azole drugs. Eventually, a metabolomic study of the GC/MS composition of these oils allowed us to develop a statistical tool which could help to select interesting antifungal products. This work thus demonstrates the major interest of the two strategies – ethnopharmacology and bioinspiration – for the search of new bioactive compounds.

http://www.theses.fr/2011AGUY0415/document

Éditeur(s) : HAL CCSD
Résumé : International audience
Obesity is currently an increasing public health problem. The intra-uterine environment plays a critical role in foetal development. The objective of this study is to investigate the association of obesity with modifications in the metabolic profiles of pregnant women, and their new-borns. Based on the PELAGIE cohort (Brittany, France), a sample of 321 pregnant women was divided into three groups according to their body mass index (BMI) (normal, over-weight and obese). Nuclear magnetic resonance-based metabolomics analyses were performed on maternal urine and cord-blood samples. Partial least squares regression-discriminant analysis (PLS-DA), polytomous and logistic regressions were used to differentiate the metabolic profiles of the three BMI groups after adjusting for potential confounders. Specific profiles were observed for the overweight and obese women (BMI > 25) compared to the normal-weight women: they had a decrease in urinary hippurate excretion associated with a decrease in phenylalanine and an increase in creatinine. We also showed an increase in the urinary excretion of lactate, citrate, acetate, creatine, and lysine only in obese women (BMI > 30) compared to the normal-weight women. The PLS-DA modelling did not reveal any significant difference between the cord-blood metabolic profiles of newborns according to maternal BMI—although infants born of obese women had a higher birth weight and a lower Apgar score. Our results confirmed the potential link between obesity and gut microbiota disruption (changes in urinary acids), as well as energy and amino-acid metabolism but did not reveal any disruption among newborns.
Metabolomics

Droits : info:eu-repo/semantics/OpenAccess
hal-01195742
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01195742
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01195742/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01195742/file/Impact%20of%20maternal%20obesity_accepted.pdf
DOI : 10.1007/s11306-015-0836-1

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: The meiotic developmental pathway in yeast enables both differentiation of vegetative cells into haploid spores that ensure long-term survival, and recombination of the parental DNA to create genetic diversity. Despite the importance of proper metabolic regulation for the supply of building blocks and energy, little is known about the reprogramming of central metabolic pathways in meiotically differentiating cells during passage through successive developmental stages. Results: Metabolic regulation during meiotic differentiation in budding yeast was analyzed by integrating information on genome-wide transcriptional activity, 26 enzymatic activities in the central metabolism, the dynamics of 67 metabolites, and a metabolic flux analysis at mid-stage meiosis. Analyses of mutants arresting sporulation at defined stages demonstrated that metabolic reprogramming is tightly controlled by the progression through the developmental pathway. The correlation between transcript levels and enzymatic activities in the central metabolism varies significantly in a developmental stage-dependent manner. The complete loss of phosphofructokinase activity at mid-stage meiosis enables a unique setup of the glycolytic pathway which facilitates carbon flux repartitioning into synthesis of spore wall precursors during the co-assimilation of glycogen and acetate. The need for correct homeostasis of purine nucleotides during the meiotic differentiation was demonstrated by the sporulation defect of the AMP deaminase mutant amd1, which exhibited hyper-accumulation of ATP accompanied by depletion of guanosine nucleotides. Conclusions: Our systems-level analysis shows that reprogramming of the central metabolism during the meiotic differentiation is controlled at different hierarchical levels to meet the metabolic and energetic needs at successive developmental stages.
ISSN: 1471-2180

inserm-01094132
http://www.hal.inserm.fr/inserm-01094132
http://www.hal.inserm.fr/inserm-01094132/document
http://www.hal.inserm.fr/inserm-01094132/file/s12915-014-0060-x.pdf
DOI : 10.1186/s12915-014-0060-x