During an immune response, metabolism changes dramatically. Metabolites are oxidized to power immune cell functions, serve as building blocks for proliferation, and act as effectors to regulate pathog...

PODCAST Le prix Francqui, considéré comme la plus haute distinction scientifique belge, vient couronner cette année les recherches menées depuis vingt ans par le professeur Patrice Cani, chercheur au Louvain Drug Research Institute. Sa spécialité: le microbiote intestinal. Le scientifique s’est imposé au fil de sa carrière comme l’un des grands spécialistes de cet univers microscopique peuplé de milliards de bactéries.

In this issue of Blood, Himonas et al1 identify antifungal agents as potent inhibitors of mitochondrial metabolism in acute myeloid leukemia (AML) cells, o

Protein palmitoylation is an important lipidic post-translation modification catalyzed by the zDHHC protein acyltransferases. In this issue of Cell Chemical Biology, Zhu et al. use an imaginative approach to control NRas palmitoylation and use it as a platform to identify inhibitors of protein palmitoylation.

Cell growth is controlled by mTOR signaling, but how metabolism directly regulates this pathway is unclear. Park and Kim et al. identify the linoleic acid metabolite 13-S-HODE as an endogenous inhibitor of mTOR, linking polyunsaturated fatty acid metabolism to the suppression of cancer cell and tumor growth.

Abstract. Clonal hematopoiesis (CH) — the expansion of genetic variants in blood — is a prime example of somatic evolution. Although it often precedes malignant transformation, many aspects of this pr...

Genome instability and mutagenesis are hallmarks of aging, acting as drivers of some age-associated pathologies, including cancer1-3. Somatic cells engage multiple layers of protection against mutagenesis, including detoxification of genotoxic metabolites; repair of DNA damage; and elimination of cells which suffer excessive damage4-7. In this context, the intrinsic apoptotic pathway is engaged in response to activation of the DNA damage response (DDR) and is thought to play a major role in limiting accumulation of mutations, particularly in cells that act as an origin for cancer, such as somatic stem cells8,9. However, the dissection of the relative contribution of different protective mechanisms that restrict mutagenesis in such cells is confounded by the long time frame of experiments; relatively low mutation burden in non-malignant cells; and high variance across individuals due to differences in germ line and environment. Here we employ deep whole-genome sequencing (WGS) combined with extended time-course sampling from a range of experimental mouse models to study mutation acquisition in hematopoietic stem cells (HSCs) during aging. Having validated that murine HSCs recapitulate mutation acquisition patterns observed in aged human HSCs, we made the surprising discovery that apoptosis has a negligible role in restricting mutagenesis. Instead, we found that HSC dormancy inhibits mutagenesis during normal aging, with dormant HSCs from old mice demonstrating a mutation burden akin to their young counterparts. Importantly, breaking HSC dormancy via induction of sterile inflammation led to a dramatic acceleration in mutation rate, demonstrating that non-genotoxic environmental stimuli can modulate genome stability. These findings provide new insights into the correlation between inflammation and both aging and carcinogenesis. ### Competing Interest Statement The authors have declared no competing interest.

Nature Metabolism, Published online: 04 May 2026; doi:10.1038/s42255-026-01523-xCell metabolism is a dynamic network of highly interconnected biochemical reactions. In this issue of Nature Metabolism, time-lapse analysis of the amino acid aspartate revealed an unexpected regulation of de novo pyrimidine biosynthesis by the tricarboxylic acid cycle metabolite succinate, with implications for the cell cycle and DNA damage response.

Nature Metabolism, Published online: 04 May 2026; doi:10.1038/s42255-026-01524-wSuccinate acts as a competitive inhibitor of mammalian aspartate transcarbamylase (ATCase), leading to impaired pyrimidine biosynthesis and reduced proliferation under SDH inhibition.

Succinate acts as a competitive inhibitor of mammalian aspartate transcarbamylase (ATCase), leading to impaired pyrimidine biosynthesis and reduced proliferation under SDH inhibition.