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Enhanced polyamine depletion in neuroblastoma models decreases translation of mRNA codons with adenosine in the third position, reprogramming the tumour proteome away from cell cycle progression and towards differentiation.

The role of pathogenic mitochondrial DNA (mtDNA) mutation in cancer remains to be studied. Here the authors show that high mtDNA mutation burden in lung cancer models leads to increased glycolysis but limited de novo serine synthesis, rendering sensitivity to dietary serine and glycine deprivation.

An inadequate supply of cofactors often limits the production of target molecules in metabolic engineering. Here, the authors report cofactor engineering through decompartmentalization of the yeast mitochondrial metabolism to improve succinic acid production in Issatchenkia orientalis.

Ghergurovich, Xu and Wang et al. show that methionine synthase is important for tumour cell survival through the generation of tetrahydrofolate rather than methionine.

Mammalian mitochondria use folate-bound one-carbon units generated by the enzyme SHMT2 to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.

The narrow frequency response of quantum harmonic oscillators typically limits their application in radiofrequency electric field detection. Now motional Raman transitions in trapped ions are shown to enable wideband, high-precision radiofrequency field sensing.

Identification of an improved glucose-6-phosphate dehydrogenase (G6PD) inhibitor G6PDi-1 blocks G6PD activity more robustly than the widely cited antagonist DHEA. G6PDi-1 treatment blocks T cell cytokine production and neutrophil oxidative burst.

Cancer cells rely on NADPH to manage oxidative stress and support biosynthesis. Here, the authors show that glucose-6-phosphate dehydrogenase (G6PD) ablation suppresses KRAS-driven lung tumours with LKB1 deficiency, but not with P53 deficiency, by impairing NADPH production, suggesting a potential therapeutic strategy.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.

White and colleagues identify a role for host autophagy in restraining T-cell-dependent immune responses, specifically against tumors with high mutational burden.

Iso-imaging integrates stable-isotope infusions with imaging mass spectrometry to enable quantitative analysis of metabolic activity in mammalian tissues with spatial resolution. IsoScope software facilitates analysis of iso-imaging data.

Metabolic labeling experiments on fermenting yeast revealed that ethanol is oxidized to acetaldehyde and acetyl-CoA and is also a major source of NADH and NADPH, demonstrating that ethanol can be consumed as a TCA cycle and redox fuel.

Aerobic glycolysis is a hallmark of fast-growing cells, but it is unclear whether glycolysis was selected for its speed. Glycolysis produces ATP slower than respiration (per protein mass) and is beneficial for rendering cells robust to hypoxia.

MISO (MultI-modal Spatial Omics) integrates two or more spatial omics modalities, despite differences in data quality and spatial resolution for improved feature extraction and clustering to reveal biologically meaningful tissue organization.

Liver and adipose tissue are shown to use different metabolic routes to generate NADPH for de novo lipogenesis, with the liver relying on a unique cytosolic serine catabolic pathway involving the enzyme SHMT1.

Munger et al. show that infection with human cytomegalovirus upregulates fatty acid biosynthesis and that pharmacological inhibition of this pathway inhibits replication of both this virus and influenza A. This approach, the first to reliably map major carbon fluxes in mammalian cells, extends the promise of metabolomics from diagnostic applications to identification of new therapeutic concepts.

Elevated plasma branched-chain amino acid (BCAA) levels have been associated with insulin resistance and type 2 diabetes. Blair et al. show that altering BCAA oxidation in skeletal muscle or liver does not influence insulin sensitivity in male mice, despite the effects on BCAA plasma levels.

The role of TREM1 in neurodegenerative diseases is unclear. Here the authors show that TREM1 promotes cognitive decline in aging and in the context of amyloid pathology in a mouse model of Alzheimer disease.

Chini et al. demonstrate that CD38⁺ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38⁺ affects intracellular NAD⁺ levels in vivo by hydrolyzing the NAD⁺ intermediate nicotinamide mononucleotide extracellularly.

Enerbäck and Rabinowitz summarize emerging evidence that lactate serves as a universal circulating fuel for mammalian cells.

The NetID algorithm annotates untargeted LC-MS metabolomics data by combining known biochemical and metabolomic principles with a global network optimization strategy.

Arany and colleagues integrate metabolomics data, tissue RNA-sequencing data and proteomics data from explanted hearts of patients with end-stage heart failure to provide a comprehensive ‘multi-omic’ evaluation of the metabolic pathways affected by heart failure.

While glucose homeostasis in the circulation is tightly controlled by insulin and other hormones, dedicated hormonal regulators do not exist for most other circulating metabolites. Using perturbative metabolite infusions with isotope labelling in mice, Li et al. show that homeostasis of many circulating metabolites is considerably regulated through mass action-driven oxidation.

The dihydrofolate reductase inhibitor, fluorofolin, shows potent activity against Pseudomonas aeruginosa and selectively eliminates P. aeruginosa from mixed-species bacterial cultures.

Different nutrient limitations slow down Escherichia coli translation via distinct mechanisms: P limitation leads to fewer ribosomes; N limitation reduces translation elongation via ribosome stalling; and C limitation is characterized by inactive ribosomes not bound to mRNA.

As solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP.

Culbertson et al. profile antisense RNAs using a newly developed computational pipeline and identify NQO1-AS as contributor to breast cancer progression and lung metastasis through regulation of the redox enzyme NQO1.

The molecule succinate, which is a product of metabolism, promotes heat production and therefore calorie burning in brown fat in mice. This discovery could have implications for combating obesity in humans.

A genetic mouse model is used to reveal a two-pronged mechanism of fructose-induced de novo lipogenesis in the liver, in which fructose catabolism in hepatocytes provides a signal to promote lipogenesis, whereas fructose metabolism by the gut microbiota provides acetate as a substrate to feed lipogenesis.

Bisphosphoglycerate mutase (BPGM) drives phosphoglycerate mutase 1 (PGAM1) phosphorylation, which is required for glycolytic flux. Loss of BPGM is partially compensated by 1,3-BPG directly phosphorylating PGAM1, sustaining glycolytic flux but diverting metabolites for serine synthesis.

Microbial production of succinic acid at an industrially relevant scale has been hindered by high downstream processing costs arising from neutral pH fermentation. Here, the authors report an end-to-end pipeline for succinic acid production at low pH using engineered acid-tolerant Issatchenkia orientalis strain.

Cerebral ischemia activates innate immune responses in injured brain lesions. Andreasson and colleagues show TREM1 is upregulated after stroke and amplifies these proinflammatory responses by peripheral CD11b⁺ myeloid cells in both the ischemic brain and distally in the intestine.

In aged mice, inhibition of prostaglandin E₂ (PGE₂) signalling through its receptor EP2 improves cellular bioenergetics, reduces inflammatory responses and restores hippocampal plasticity to youthful levels, resulting in an improvement in spatial memory and cognition.

The oxidative pentose-phosphate pathway (oxPPP) is a major NADPH producer. Here the authors show that malic enzyme or isocitrate dehydrogenase can support the growth of cells lacking the oxPPP, but the oxPPP is necessary to maintain a normal NADPH/NADP ratio, DHFR activity and folate metabolism.