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Article
Open AccessAncestral allele of DNA polymerase gamma modifies antiviral tolerance
Mitochondria are critical modulators of antiviral tolerance through the release of mitochondrial RNA and DNA (mtDNA and mtRNA) fragments into the cytoplasm after infection, activating virus sensors and type-I ...
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Article
Open AccessMetabolic landscape of the male mouse gut identifies different niches determined by microbial activities
Distinct niches of the mammalian gut are populated by diverse microbiota, but the contribution of spatial variation to intestinal metabolism remains unclear. Here we present a map of the longitudinal metabolom...
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Article
Open AccessIntegrated multi-omics reveals anaplerotic rewiring in methylmalonyl-CoA mutase deficiency
Methylmalonic aciduria (MMA) is an inborn error of metabolism with multiple monogenic causes and a poorly understood pathogenesis, leading to the absence of effective causal treatments. Here we employ multi-la...
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Article
Open AccessTargeting lactate dehydrogenase B-dependent mitochondrial metabolism affects tumor initiating cells and inhibits tumorigenesis of non-small cell lung cancer by inducing mtDNA damage
Once considered a waste product of anaerobic cellular metabolism, lactate has been identified as a critical regulator of tumorigenesis, maintenance, and progression. The putative primary function of lactate de...
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Article
Open AccessADAMTS18+ villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels
The small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from the early 1970s uncovered unusual spatial...
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Article
Open AccessMSNovelist: de novo structure generation from mass spectra
Current methods for structure elucidation of small molecules rely on finding similarity with spectra of known compounds, but do not predict structures de novo for unknown compound classes. We present MSNovelis...
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Article
Open AccessDietary excess regulates absorption and surface of gut epithelium through intestinal PPARα
Intestinal surface changes in size and function, but what propels these alterations and what are their metabolic consequences is unknown. Here we report that the food amount is a positive determinant of the gu...
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Article
Mass spectrometry-based metabolomics: a guide for annotation, quantification and best reporting practices
Mass spectrometry-based metabolomics approaches can enable detection and quantification of many thousands of metabolite features simultaneously. However, compound identification and reliable quantification are...
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Article
Open AccessThe coenzyme thiamine diphosphate displays a daily rhythm in the Arabidopsis nucleus
In plants, metabolic homeostasis—the driving force of growth and development—is achieved through the dynamic behavior of a network of enzymes, many of which depend on coenzymes for activity. The circadian cloc...
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Article
Lipid signalling drives proteolytic rewiring of mitochondria by YME1L
Reprogramming of mitochondria provides cells with the metabolic flexibility required to adapt to various developmental transitions such as stem cell activation or immune cell reprogramming, and to respond to e...
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Article
Open AccessYin Yang 1 sustains biosynthetic demands during brain development in a stage-specific manner
The transcription factor Yin Yang 1 (YY1) plays an important role in human disease. It is often overexpressed in cancers and mutations can lead to a congenital haploinsufficiency syndrome characterized by cran...
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Article
Open AccessThe thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation
The thioredoxin-1 (Trx1) system is an important contributor to cellular redox balance and is a sensor of energy and glucose metabolism. Here we show critical c-Myc-dependent activation of the Trx1 system durin...
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Article
Open AccessAn integrative metabolomics and transcriptomics study to identify metabolic alterations in aged skin of humans in vivo
Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterati...
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Article
Nontargeted in vitro metabolomics for high-throughput identification of novel enzymes in Escherichia coli
A method to screen proteins for enzymatic activity by incubating purified or overexpressed proteins with a metabolite extract and measuring changes in metabolite abundance using mass spectrometry enables high-...
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Article
Open AccessBranched-chain amino acid catabolism is a conserved regulator of physiological ageing
Ageing has been defined as a global decline in physiological function depending on both environmental and genetic factors. Here we identify gene transcripts that are similarly regulated during physiological ag...
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Article
Real-time metabolome profiling of the metabolic switch between starvation and growth
With a method involving the rapid injection of living cells into a mass spectrometer, researchers demonstrate the ability to monitor metabolite profiles in real time over the course of several hours.
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Article
HIF-driven SF3B1 induces KHK-C to enforce fructolysis and heart disease
Fructose is a major component of dietary sugar and its overconsumption exacerbates key pathological features of metabolic syndrome. The central fructose-metabolising enzyme is ketohexokinase (KHK), which exist...
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Article
Open AccessD-Glucosamine supplementation extends life span of nematodes and of ageing mice
D-Glucosamine (GlcN) is a freely available and commonly used dietary supplement potentially promoting cartilage health in humans, which also acts as an inhibitor of glycolysis. Here we show that GlcN, independe.....
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Article
Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis
Adult neural stem and progenitor cells (NSPCs) show high levels of fatty acid synthase (Fasn)-dependent de novo lipogenesis, a process that is controlled by Spot14 to regulate the rate of proliferation; this indi...
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Article
A high-throughput metabolomics method to predict high concentration cytotoxicity of drugs from low concentration profiles
A major source of drug attrition in pharmacological development is drug toxicity, which eventually manifests itself in detrimental physiological effects. These effects can be assessed in large sample cohorts, ...
