| 1. |
- Correia-Melo, Clara, et al.
(författare)
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Cell-cell metabolite exchange creates a pro-survival metabolic environment that extends lifespan
- 2023
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 186:1, s. 63-79.e21
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Tidskriftsartikel (refereegranskat)abstract
- Metabolism is deeply intertwined with aging. Effects of metabolic interventions on aging have been explained with intracellular metabolism, growth control, and signaling. Studying chronological aging in yeast, we reveal a so far overlooked metabolic property that influences aging via the exchange of metabolites. We observed that metabolites exported by young cells are re-imported by chronologically aging cells, resulting in cross-generational metabolic interactions. Then, we used self-establishing metabolically cooperating communities (SeMeCo) as a tool to increase metabolite exchange and observed significant lifespan extensions. The longevity of the SeMeCo was attributable to metabolic reconfigurations in methionine consumer cells. These obtained a more glycolytic metabolism and increased the export of protective metabolites that in turn extended the lifespan of cells that supplied them with methionine. Our results establish metabolite exchange interactions as a determinant of cellular aging and show that metabolically cooperating cells can shape the metabolic environment to extend their lifespan.
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| 2. |
- Nielsen, Jens B, 1962
(författare)
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Antibiotic Lethality Is Impacted by Nutrient Availabilities: New Insights from Machine Learning
- 2019
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 177:6, s. 1373-1374
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this issue of Cell, Yang, Wright et al. describe a machine learning approach that that can provide mechanistic insight from chemical screens. They use this approach to uncover how the nutritional availability for Escherichia coli impacts lethality toward three widely used antibiotics.
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| 3. |
- Nielsen, Jens B, 1962
(författare)
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Bioactive metabolites: The double-edged sword in your food
- 2022
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 185:24, s. 4469-4471
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Food contains many different bioactive metabolites that interact with human metabolism. Many of these have health benefits, but in this issue of Cell, researchers show that the gut microbiome can convert a bioactive metabolite to metabolites that may elevate the risks of developing cardiovascular disease.
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| 4. |
- Nielsen, Jens B, 1962, et al.
(författare)
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Engineering Cellular Metabolism
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 164:6, s. 1185-1197
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Forskningsöversikt (refereegranskat)abstract
- Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation.
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| 5. |
- Qin, Ning, 1990, et al.
(författare)
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Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast
- 2023
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 186:4, s. 748-763.e15
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Tidskriftsartikel (refereegranskat)abstract
- Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.
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| 6. |
- Sampson, Timothy R, et al.
(författare)
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Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease.
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 167:6, s. 1469-1480.e12
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD-affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.
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| 7. |
- Weinberg, R. A., et al.
(författare)
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All You Need Is Mentorship
- 2016
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 164:6, s. 1092-1093
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 8. |
- Yu, Tao, 1986, et al.
(författare)
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Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis
- 2018
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 174:6, s. 1549-1572
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Tidskriftsartikel (refereegranskat)abstract
- Engineering microorganisms for production of fuels and chemicals often requires major re-programming of metabolism to ensure high flux toward the product of interest. This is challenging, as millions of years of evolution have resulted in establishment of tight regulation of metabolism for optimal growth in the organism's natural habitat. Here, we show through metabolic engineering that it is possible to alter the metabolism of Saccharomyces cerevisiae from traditional ethanol fermentation to a pure lipogenesis metabolism, resulting in high-level production of free fatty acids. Through metabolic engineering and process design, we altered subcellular metabolic trafficking, fine tuned NADPH and ATP supply, and decreased carbon flux to biomass, enabling production of 33.4 g/L extracellular free fatty acids. We further demonstrate that lipogenesis metabolism can replace ethanol fermentation by deletion of pyruvate decarboxylase enzymes followed by adaptive laboratory evolution. Genome sequencing of evolved strains showed that pyruvate kinase mutations were essential for this phenotype.
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