Renal Coenzyme A (CoA) Production Fuels Stem Cell Proliferation and Tumor Growth

Coenzyme A (CoA), derived from Vitamin B5 (VB5), is essential for lipid metabolism, energy production, and cell proliferation. While the intracellular functions of CoA are well characterized, its tissue-specific regulation and systemic physiological roles remain poorly understood. Here, using Drosophila melanogaster, we uncover a gut-renal circuit in which dietary VB5 stimulates CoA biosynthesis specifically in the Malpighian tubules (MTs, the fly kidney), non-autonomously impacting gut homeostasis. We show that Myc boosts renal CoA production by directly upregulating Fbl (PANK1-3 homolog) and downregulating dPANK4 in the MTs. Elevated CoA biosynthesis enhances the mevalonate-isoprenoid pathway activity in the gut, promoting intestinal stem cell proliferation. We further demonstrate that renal CoA production is required for gut tumor growth in a fly model. Consistently, MYC and genes within the CoA-isoprenoid axis display strong association with clinical outcomes in human cancers. Together, our findings establish that Myc-driven CoA metabolism generates an inter-organ signal that couples VB5 availability to stem cell control and tumor growth, and identify the CoA-isoprenoid axis as a targetable metabolic vulnerability in cancer.