scholarly journals Organellar Evolution: A Path from Benefit to Dependence

2022 ◽  
Vol 10 (1) ◽  
pp. 122
Author(s):  
Miroslav Oborník
Keyword(s):  
Cell Survival ◽  
Metabolic Pathway ◽  
Environmental Conditions ◽  
Metabolic Pathways ◽  
Host Cells ◽  
Anaerobic Conditions ◽  
Mutual Dependence ◽  
Metabolic Functions ◽  
Gradual Shift

Eukaryotic organelles supposedly evolved from their bacterial ancestors because of their benefits to host cells. However, organelles are quite often retained, even when the beneficial metabolic pathway is lost, due to something other than the original beneficial function. The organellar function essential for cell survival is, in the end, the result of organellar evolution, particularly losses of redundant metabolic pathways present in both the host and endosymbiont, followed by a gradual distribution of metabolic functions between the organelle and host. Such biological division of metabolic labor leads to mutual dependence of the endosymbiont and host. Changing environmental conditions, such as the gradual shift of an organism from aerobic to anaerobic conditions or light to dark, can make the original benefit useless. Therefore, it can be challenging to deduce the original beneficial function, if there is any, underlying organellar acquisition. However, it is also possible that the organelle is retained because it simply resists being eliminated or digested untill it becomes indispensable.

scholarly journals PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 164
Author(s):  
Federica Costa ◽  
Valentina Marchica ◽  
Paola Storti ◽  
Fabio Malavasi ◽  
Nicola Giuliani
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Survival ◽  
Immune Suppression ◽  
Metabolic Pathways ◽  
Therapeutic Strategy ◽  
Myeloma Cell ◽  
Immune Microenvironment ◽  
Potential Use

The emerging role of the PD-1/PD-L1 axis in MM immune-microenvironment has been highlighted by several studies. However, discordant data have been reported on PD-1/PD-L1 distribution within the bone marrow (BM) microenvironment of patients with monoclonal gammopathies. In addition, the efficacy of PD-1/PD-L1 blockade as a therapeutic strategy to reverse myeloma immune suppression and inhibit myeloma cell survival still remains unknown. Recent data suggest that, among the potential mechanisms behind the lack of responsiveness or resistance to anti-PD-L1/PD-1 antibodies, the CD38 metabolic pathways involving the immune-suppressive factor, adenosine, could play an important role. This review summarizes the available data on PD-1/PD-L1 expression in patients with MM, reporting the main mechanisms of regulation of PD-1/PD-L1 axis. The possible link between the CD38 and PD-1/PD-L1 pathways is also reported, highlighting the rationale for the potential use of a combined therapeutic approach with CD38 blocking agents and anti-PD-1/PD-L1 antibodies in order to improve their anti-tumoral effect in MM patients.

IDENTIFYING RELEVANT PATHWAYS AND BIOMARKERS IN CROHN’S DISEASE USING CONTEXTUALIZED METABOLIC NETWORK MODEL

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S9-S10
Author(s):  
Brooklyn McGrew ◽  
Aman Shrivastava ◽  
Philip Fernandes ◽  
Lubaina Ehsan ◽  
Yash Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Fatty Acid ◽  
Crohn's Disease ◽  
Fatty Acid Synthesis ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Acid Synthesis ◽  
Transcriptomic Data ◽  
Context Specific

Abstract Background Candidate markers for Crohn’s Disease (CD) may be identified via gene expression-based construction of metabolic networks (MN). These can computationally describe gene-protein-reaction associations for entire tissues and also predict the flux of reactions (rate of turnover of specific molecules via a metabolic pathway). Recon3D is the most comprehensive human MN to date. We used publicly available CD transcriptomic data along with Recon3D to identify metabolites as potential diagnostic and prognostic biomarkers. Methods Terminal ileal gene expression profiles (36,372 genes; 218 CD. 42 controls) from the RISK cohort (Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease) and their transcriptomic abundances were used. Recon3D was pruned to only include RISK dataset transcripts which determined metabolic reaction linkage with transcriptionally active genes. Flux balance analysis (FBA) was then run using RiPTiDe with context specific transcriptomic data to further constrain genes (Figure 1). RiPTiDe was independently run on transcriptomic data from both CD and controls. From the pruned and constricted MN obtained, reactions were extracted for further analysis. Results After applying the necessary constraints to modify Recon3D, 527 CD and 537 control reactions were obtained. Reaction comparison with a publicly available list of healthy small intestinal epithelial reactions (n=1282) showed an overlap of 80 CD and 84 control reactions. These were then further grouped based on their metabolic pathways. RiPTiDe identified context specific metabolic pathway activity without supervision and the percentage of forward, backward, and balanced reactions for each metabolic pathway (Figure 2). The metabolite concentrations in the small intestine was altered among CD patients. Notably, the citric acid cycle and malate-aspartate shuttle were affected, highlighting changes in mitochondrial metabolic pathways. This is illustrated by changes in the number of reactions at equilibrium between CD and control. Conclusions The results are relevant as cytosolic acetyl-CoA is needed for fatty acid synthesis and is obtained by removing citrate from the citric acid cycle. An intermediate removal from the cycle has significant cataplerotic effects. The malate-aspartate shuttle also allows electrons to move across the impermeable membrane in the mitochondria (fatty acid synthesis location). These findings are reported by previously published studies where gene expression for fatty acid synthesis is altered in CD patients along with mitochondrial metabolic pathway changes, resulting in altered cell homeostasis. In-depth analysis is currently underway with our work supporting the utility of potential metabolic biomarkers for CD diagnosis, management and improved care.

Metabolite utilization by isolated embryonic rat hearts in vitro

Development ◽  
1972 ◽  
Vol 28 (2) ◽  
pp. 235-245
Author(s):  
Steven J. Cox ◽  
David L. Gunberg
Keyword(s):  
Metabolic Pathways ◽  
Maximum Rate ◽  
Contractile Activity ◽  
Cardiac Contraction ◽  
Anaerobic Conditions ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Aerobic And Anaerobic ◽  
Aerobic And Anaerobic Conditions

Isolated hearts from 11-, 12- and 13-day rat embryos were incubated in a simple defined salt solution to which was added a variety of single substrates. Utilization of the added substrate was determined by comparing the contractile rates of the hearts in the presence and absence of the compound being tested. Of all the compounds tested only those involved in the Embden-Meyerhof glycolytic pathway were capable of maintaining cardiac contraction at a maximum rate in the 11-day heart. This was accomplished under both aerobic and anaerobic conditions. Although glycolysis remained important, the 12- and 13-day hearts exhibited a shift in dependence towards other metabolic pathways. This conclusion was based on the observations that anaerobic glycolysis could no longer maintain maximum heart rates and that a variety of non-glycolytic compounds could be utilized for contractile activity by the 12- and 13-day organs.

scholarly journals Metabolism of a 5-nitroimidazole in susceptible and resistant isogenic strains of Bacteroides fragilis.

1997 ◽  
Vol 41 (7) ◽  
pp. 1495-1499 ◽  
Author(s):  
J P Carlier ◽  
N Sellier ◽  
M N Rager ◽  
G Reysset
Keyword(s):  
Metabolic Pathways ◽  
Enzymatic Reaction ◽  
Bacteroides Fragilis ◽  
Susceptible Strain ◽  
Ring Cleavage ◽  
Anaerobic Conditions ◽  
Resting Cell ◽  
Electron Reduction ◽  
Classical Reduction ◽  
Isogenic Strains

We investigated the metabolism of dimetridazole (1,2-dimethyl-5-nitroimidazole) (DMZ) by the resting cell method in a susceptible strain of Bacteroides fragilis and in the same strain containing the nimA gene, which conferred resistance to 5-nitroimidazole drugs. In both cases, under strict anaerobic conditions DMZ was metabolized without major ring cleavage or nitrate formation. However, one of two distinct metabolic pathways is involved, depending on the susceptibility of the strain. In the susceptible strain, the classical reduction pathway of nitroaromatic compounds is followed at least as far as the nitroso-radical anion, with further formation of the azo-dimer: 5,5'-azobis-(1,2-dimethylimidazole). In the resistant strain, DMZ is reduced to the amine derivative, namely, 5-amino-1,2-dimethylimidazole, preventing the formation of the toxic form of the drug. The specificity of the six-electron reduction of the nitro group, which is restricted to 4- and 5-nitroimidazole, suggests an enzymatic reaction. We thus conclude that nimA and related genes may encode a 5-nitroimidazole reductase.

scholarly journals MicroRNAs and Mammarenaviruses: Modulating Cellular Metabolism

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2525
Author(s):  
Jorlan Fernandes ◽  
Renan Lyra Miranda ◽  
Elba Regina Sampaio de Lemos ◽  
Alexandro Guterres
Keyword(s):  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Mirna Expression Profile ◽  
Metabolic Reprogramming ◽  
Host Cells ◽  
Emerging Viruses ◽  
Cellular Mirnas ◽  
Host Interactions ◽  
Causative Agents

Mammarenaviruses are a diverse genus of emerging viruses that include several causative agents of severe viral hemorrhagic fevers with high mortality in humans. Although these viruses share many similarities, important differences with regard to pathogenicity, type of immune response, and molecular mechanisms during virus infection are different between and within New World and Old World viral infections. Viruses rely exclusively on the host cellular machinery to translate their genome, and therefore to replicate and propagate. miRNAs are the crucial factor in diverse biological processes such as antiviral defense, oncogenesis, and cell development. The viral infection can exert a profound impact on the cellular miRNA expression profile, and numerous RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Our present study indicates that mammarenavirus infection induces metabolic reprogramming of host cells, probably manipulating cellular microRNAs. A number of metabolic pathways, including valine, leucine, and isoleucine biosynthesis, d-Glutamine and d-glutamate metabolism, thiamine metabolism, and pools of several amino acids were impacted by the predicted miRNAs that would no longer regulate these pathways. A deeper understanding of mechanisms by which mammarenaviruses handle these signaling pathways is critical for understanding the virus/host interactions and potential diagnostic and therapeutic targets, through the inhibition of specific pathologic metabolic pathways.

scholarly journals Genome analyses of a placozoan rickettsial endosymbiont show a combination of mutualistic and parasitic traits

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kai Kamm ◽  
Hans-Jürgen Osigus ◽  
Peter F. Stadler ◽  
Rob DeSalle ◽  
Bernd Schierwater
Keyword(s):  
Amino Acids ◽  
Environmental Conditions ◽  
Metabolic Pathways ◽  
Essential Amino Acids ◽  
Intracellular Bacteria ◽  
The Novel ◽  
Symbiotic Relationships ◽  
Genome Analyses ◽  
Growth And Reproduction

AbstractSymbiotic relationships between eukaryotic hosts and bacteria range from parasitism to mutualism and may deeply influence both partners’ fitness. The presence of intracellular bacteria in the metazoan phylum Placozoa has been reported several times, but without any knowledge about the nature of this relationship and possible implications for the placozoan holobiont. This information may be of crucial significance since little is known about placozoan ecology and how different species adapt to different environmental conditions, despite being almost invariable at the morphological level. We here report on the novel genome of the rickettsial endosymbiont of Trichoplax sp. H2 (strain “Panama”). The combination of eliminated and retained metabolic pathways of the bacterium indicates a potential for a mutualistic as well as for a parasitic relationship, whose outcome could depend on the environmental context. In particular we show that the endosymbiont is dependent on the host for growth and reproduction and that the latter could benefit from a supply with essential amino acids and important cofactors. These findings call for further studies to clarify the actual benefit for the placozoan host and to investigate a possible role of the endosymbiont for ecological separation between placozoan species.

scholarly journals Untargeted Metabolomics Identifies Key Metabolic Pathways Altered by Thymoquinone in Leukemic Cancer Cells

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1792 ◽  
Author(s):  
Asma Ahmed AlGhamdi ◽  
Mohammed Razeeth Shait Mohammed ◽  
Mazin A. Zamzami ◽  
Abdulrahman L. Al-Malki ◽  
Mohamad Hasan Qari ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Nigella Sativa ◽  
Experimental Studies ◽  
Nucleotide Metabolism ◽  
Untargeted Metabolomics ◽  
Sphingolipid Metabolism ◽  
Cancer Cell Survival

Thymoquinone (TQ), a naturally occurring anticancer compound extracted from Nigella sativa oil, has been extensively reported to possess potent anti-cancer properties. Experimental studies showed the anti-proliferative, pro-apoptotic, and anti-metastatic effects of TQ on different cancer cells. One of the possible mechanisms underlying these effects includes alteration in key metabolic pathways that are critical for cancer cell survival. However, an extensive landscape of the metabolites altered by TQ in cancer cells remains elusive. Here, we performed an untargeted metabolomics study using leukemic cancer cell lines during treatment with TQ and found alteration in approximately 335 metabolites. Pathway analysis showed alteration in key metabolic pathways like TCA cycle, amino acid metabolism, sphingolipid metabolism and nucleotide metabolism, which are critical for leukemic cell survival and death. We found a dramatic increase in metabolites like thymine glycol in TQ-treated cancer cells, a metabolite known to induce DNA damage and apoptosis. Similarly, we observed a sharp decline in cellular guanine levels, important for leukemic cancer cell survival. Overall, we provided an extensive metabolic landscape of leukemic cancer cells and identified the key metabolites and pathways altered, which could be critical and responsible for the anti-proliferative function of TQ.

scholarly journals Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1

2010 ◽  
Vol 190 (1) ◽  
pp. 143-157 ◽  
Author(s):  
Adrian Mehlitz ◽  
Sebastian Banhart ◽  
André P. Mäurer ◽  
Alexis Kaushansky ◽  
Andrew G. Gordus ◽  
...  
Keyword(s):  
Cell Survival ◽  
Host Cell ◽  
Early Phase ◽  
Protein Microarray ◽  
Critical Role ◽  
Adaptor Protein ◽  
Effector Proteins ◽  
Host Cells ◽  
Cell Functions ◽  
Induced Apoptosis

Many bacterial pathogens translocate effector proteins into host cells to manipulate host cell functions. Here, we used a protein microarray comprising virtually all human SRC homology 2 (SH2) and phosphotyrosine binding domains to comprehensively and quantitatively assess interactions between host cell proteins and the early phase Chlamydia trachomatis effector protein translocated actin-recruiting phosphoprotein (Tarp), which is rapidly tyrosine phosphorylated upon host cell entry. We discovered numerous novel interactions between human SH2 domains and phosphopeptides derived from Tarp. The adaptor protein SHC1 was among Tarp’s strongest interaction partners. Transcriptome analysis of SHC1-dependent gene regulation during infection indicated that SHC1 regulates apoptosis- and growth-related genes. SHC1 knockdown sensitized infected host cells to tumor necrosis factor–induced apoptosis. Collectively, our findings reveal a critical role for SHC1 in early C. trachomatis–induced cell survival and suggest that Tarp functions as a multivalent phosphorylation-dependent signaling hub that is important during the early phase of chlamydial infection.

scholarly journals Metabolic Pathway Genes Associated with Susceptibility Genes to Coronary Artery Disease

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Heng Lu ◽  
Yi Chen ◽  
Linlin Li
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Blood Lipids ◽  
Single Gene ◽  
Susceptibility Genes ◽  
Metabolic Factors ◽  
Citrate Cycle ◽  
Artery Disease

Coronary artery disease (CAD) is one of the leading threats to global health. Previous research has proven that metabolic pathway disorders, such as high blood lipids and diabetes, are one of the risk factors that mostly cause CAD. However, the crosstalk between metabolic pathways and CAD was mostly studied on physiology processes by analyzing a single gene function. A canonical correlation analysis was used to identify the metabolic pathways, which were integrated as a unit to coexpress with CAD susceptibility genes, and to resolve additional metabolic factors that are related to CAD. Seven pathways, including citrate cycle, ubiquinone, terpenoid quinone biosynthesis, and N-glycan biosynthesis, were identified as an integrated unit coexpressed with CAD genes. These pathways could not be revealed as a coexpressed pathway through traditional methods as each single gene has weak correlation. Furthermore, sets of genes in these pathways were candidate markers for diagnosis and detection from patients’ serum.

scholarly journals An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Mengting Liu ◽  
Liying Tang ◽  
Xin Liu ◽  
Jing Fang ◽  
Hao Zhan ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Metabolic Network ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Evidence Based ◽  
Kegg Database ◽  
Pathway Enrichment ◽  
Network Research

In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers.

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