A distinct Acyl-CoA binding protein (ACBP6) shapes tissue plasticity during nutrient adaptation in Drosophila

Abstract

Nutrient availability is a major selective force in the evolution of metazoa, and thus plasticity in tissue function and morphology is shaped by adaptive responses to nutrient changes. Utilizing Drosophila, we reveal that distinct calibration of acyl-CoA metabolism, mediated by Acbp6 (Acyl-CoA binding-protein 6), is critical for nutrient-dependent tissue plasticity. Drosophila Acbp6, which arose by evolutionary duplication and binds acyl-CoA to tune acetyl-CoA metabolism, is required for intestinal resizing after nutrient deprivation through activating intestinal stem cell proliferation from quiescence. Disruption of acyl-CoA metabolism by Acbp6 attenuation drives aberrant ‘switching’ of metabolic networks in intestinal enterocytes during nutrient adaptation, impairing acetyl-CoA metabolism and acetylation amid intestinal resizing. We also identified STAT92e, whose function is influenced by acetyl-CoA levels, as a key regulator of acyl-CoA and nutrient-dependent changes in stem cell activation. These findings define a regulatory mechanism, shaped by acyl-CoA metabolism, that adjusts proliferative homeostasis to coordinately regulate tissue plasticity during nutrient adaptation.

A single-cell 3D spatiotemporal multi-omics atlas fromDrosophilaembryogenesis to metamorphosis

“…Starting from E15.77, gastric caecum-specific marker genes Acbp4 and Pebp1 ranked top in genes associated with all aspects of morphometric changes (Table S8) , in line with the timing of gastric caecum extrusion and formation from the midgut chamber (∼15 h of development) 41 . In addition, multiple Acyl-CoA binding protein (Acbp) family genes demonstrated high correlation with morphometric scores in late-stage midgut, which aligned with their known function of linking nutrient sensing and shaping tissue plasticity 106 . We also observed several potential regulators or effectors of midgut morphological changes, such as CG32633 , which consistently displayed positive correlation with cell migration acceleration across samples (Figure 6P) .…”