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Todorova et al. characterize the strategies through which embryos secure amino acid supply during the early phases of development. Their findings show that, in the preimplantation phase, embryos uptake whole proteins through macropinocytosis and, over time, they shift towards soluble amino acid uptake. This strategy may contribute to protecting embryos from nutrient fluctuations.
Wei et al. show that proteolytic cleavage of fatty acid synthase (FASN) upon stress contributes to stress resolution. This role in stress resolution of the resulting C-terminal fragment of FASN is independent of its canonical function in fatty acid synthesis.
Iron is shown to have a central role in senescence, both by triggering senescence and through its accumulation in senescent cells, which is driving the senescence-associated secretory phenotype and, in turn, promotes fibrogenesis.
In this study, Papalazarou et al. screen the solute carrier family and identify candidates involved of serine transport in colorectal cancer cells. They further characterize cytosolic SLC6A14 and mitochondrial SLC25A15 as mediators of adequate serine supply to sustain cancer cell proliferation.
Shoop et al. develop mitoARCUS, a mitochondria-targeted nuclease with high specificity, to correct a relatively common pathogenic mtDNA mutation, allowing for beneficial shifts in heteroplasmy while reducing nuclear off-target gene editing.
Efferocytosis-induced macrophage proliferation is supported by increased non-canonical upregulation of glycolysis. Ngai, Schilperoort and Tabas provide mechanistic insight to understand how glycolysis-derived lactate contributes to this process by stabilizing MYC via extracellular signalling.
Hildreth et al. show that during diet-induced obesity, conventional type 1 dendritic cells (cDC1s) in white adipose tissue (WAT) take up DNA-containing apoptotic bodies from adipocytes, which triggers STING-dependent interleukin-12 production from cDC1s, contributing to WAT inflammation in mice.
In this study, Kagan et al. highlight the relevance of adequate cardiolipin homeostasis by offering mechanistic insight into the pathogenesis of Barth syndrome. The study shows how altered accumulation of mono-lyso-cardiolipin, one of the derivatives of the mitochondrial lipid cardiolipin, forms an anomalous peroxidase complex with cytochrome c, thus leading to increased oxidation of polyunsaturated phospholipids.
Kovatcheva et al. show that vitamin B12 improves the efficiency of in vivo reprogramming and tissue repair through its functions in one-carbon metabolism and epigenetic modulation.
In this study, Rabah et al. investigate glucose usage in the brain, and show how glial cells transfer glycolysis-derived alanine to neurons in a fly model, thus supporting memory formation in cholinergic circuits.
PDK4-dependent lactate production by senescent stromal cells is shown to promote cancer growth and drug resistance and might have a broader role in the emergence of age-associated diseases.
In this study, Fu et al. provide mechanistic insight into how GLUT2 fine-tunes environmental nutrient sensing with T cell activation, which optimizes metabolic adaptation during acquisition of T cell effector function.
Gut-derived ammonia mediates stress responses in the host by maintaining brain glutamine availability, uncovering a gut–brain signalling basis for emotional behaviour.
Defects in interleukin-22 production and group 3 innate lymphoid cells are correlated with aggravated gut inflammation. Wu et al. find that proline uptake via the proline transporter Slc6a7 is involved in activation of lymphoid tissue inducer cells and interleukin-22 production in the gut, and that dietary supplementation with proline alleviates colitis in a mouse model.
Guhathakurta et al. describe the acetyltransferase activity of MOF in the mitochondria. MOF can acetylate COX17, thus contributing to the assembly and function of respiratory complex IV. These findings provide better understanding of how mitochondrial function is fine-tuned by acetylation.
Miller et al. use fast thermal preservation and mass spectrometry imaging to reveal rapid neuron-layer metabolic responses to stimulation within a brain slice. Stimulation increases glucose use and converts spent ATP into metabolic fuel, via inosine.
Lundgren et al. show that in response to transient cold exposure, a distinct subpopulation of brown adipocytes carries out a lipogenic response involving production of acylcarnitines, which enables an improved thermogenic response to secondary cold exposure.
This study presents a comprehensive pipeline to profile transmembrane receptors involved in macrophage-driven inflammation in pancreatic islets during the onset of diabetes. The authors identify GPR132 as a mediator of macrophage-driven inflammation and find compounds that reduce inflammation and improve glycaemic control.