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A systematic deep-mutational-scanning analysis of the mitochondrial complex I assembly factor NDUFAF6 reveals its molecular function and aids in the identification of pathogenic variants in mitochondrial disease.
A new engineering strategy for improving the biosynthesis of secondary metabolites in Streptomyces has been developed through the analysis of genes co-evolved with biosynthetic gene clusters. This strategy has been verified in 11 Streptomyces strains to enhance production of 16,385 metabolites, showing potential applications in drug discovery and industrial production.
A new sensor that detects optoacoustic signals generated by mid-infrared light enables measurement of glucose concentration from intracutaneous tissue rich in blood. This technology does not rely on glucose measurements in interstitial fluid or blood sampling and might yield the next generation of non-invasive glucose-sensing devices for improved diabetes management.
AMPK directly phosphorylates the mitochondrial protein SYNJ2BP to facilitate its interaction with the RNA-binding protein SYNJ2a, which transports Pink1 mRNA into neurites. AMPK inhibition downstream of insulin signalling untethers Pink1 mRNA from neuronal mitochondria and favours PINK1-dependent mitophagy in neurons. ApoE4-induced insulin receptor internalization reverses the process by stabilizing Pink1 mRNA binding to neuronal mitochondria.
Individuals with osteoporosis have increased risk of Alzheimer’s disease or cognitive impairment during ageing. We elucidated a partial explanation for bone dysmetabolism’s association with such cognitive decline, by demonstrating how elevated sclerostin secretion from osteocytes in bone impaired cognitive function in aged mice and in an Alzheimer’s disease mouse model.
Glycerol-3-Phosphate (G3P) and phosphoethanolamine (pEtN) biosynthetic pathways are modulated during senescence establishment to sustain lipid droplet accumulation and senescence-associated secretome. These findings reveal new targets for an immunomodulatory approach against senescent cells.
Here, we reveal functional heterogeneity among β cells and discover that readily releasable β cells (RRβs) are a subpopulation that disproportionally contributes to biphasic glucose-stimulated insulin secretion. We further show that the dysfunction of RRβs has a crucial role in the progression of diabetes.
Murine blastocysts and embryonic stem cells mimicking the pre-implantation epiblast import extracellular protein through macropinocytosis and engage a robust lysosomal digestive programme to meet their nutrient demands. We found that as development proceeds, post-implantation epiblast-like cells downregulate protein digestion, increase expression of amino acid transporters and become dependent on soluble amino acids.
Calcium sensing receptor (CaSR) and peptide transporter 1 (PepT1) have been implicated in protein sensing in the gut, although the mechanisms are poorly understood. We find that, in the small intestine, CasR and PepT1 are necessary for protein sensing to regulate gut peptide release, feeding and glucose tolerance in rats in vivo.
