How amyloid can be a substrate of memory: Formation of memories requires changes in the molecular composition of the synapse. How these changes occur and what maintains this altered synaptic composition so that memory can persist are unknown. Hervas et al. report the structure of a synaptic translation regulator called Orb2 isolated from the brains of adult fruit flies that is important for the maintenance and recall of memory. Orb2 forms an amyloid and changes its activity from a translation repressor to an activator. The amyloid core is composed of polar hydrophilic residues, as opposed to the hydrophobic ones found in nonfunctional or pathological amyloids. The structure provides insights into how amyloids could be a stable yet malleable substrate of memory. Science , this issue p. 1230

Central carbon metabolism undergoes extensive remodeling in cancers, yet the extent to which the resulting network architectures and operating principles are conserved across species and oncogenic contexts in vivo remains unclear. Here, central carbon metabolism was evaluated in Hippo/Yki-driven Drosophila gut tumors, as Hippo-YAP/TAZ signaling links nutritional cues to metabolic state and contributes to epithelial tumorigenesis and therapy resistance. Using integrated steady-state metabolomics, transcriptomics and [U-13C6]glucose tracing, we defined how Hippo pathway activation reorganizes nutrient utilization and carbon flux in vivo and assessed how the resulting Yki-driven metabolic network aligns with mammalian cancer metabolism. Yki tumors exhibited a Warburg-like state with increased glycolytic throughput and enhanced conversion of glucose-derived carbon to lactate, accompanied by transcriptional upregulation of key glycolytic and lactate-production enzymes. Glucose carbon was also redirected into redox-supporting and anabolic nodes, including activation of the glycerol-3-phosphate shuttle and increased labeling of alanine and serine. Mitochondrial metabolism was reorganized into a non-canonical, segmented TCA network centered on α-ketoglutarate, which accumulated and acted as a drain into glutamate/glutamine and 2-hydroxyglutarate rather than supporting complete oxidative turnover. Despite reduced abundance of pentose phosphate intermediates, non-oxidative PPP carbon rearrangements and ribose labeling were maintained, enabling robust glucose contribution to pyrimidine nucleotide pools, including strongly labeled dTTP. Together, these data establish a comprehensive map of Yki-driven central carbon partitioning in vivo and highlight conserved principles of tumor carbon allocation shared across oncogenic contexts and mammalian cancer metabolism.