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bioRxiv · 10.1101/2025.08.08.669325

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

Miao, T.·Liu, Y.·Qadiri, M.·Asara, J. M.·Hu, Y.·Sun, X.·Dibble, C.·Perrimon, N.
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Abstract

Coenzyme A (CoA), derived from Vitamin B5 (VB5; also called pantothenate), is essential for lipid metabolism, energy production, and cell proliferation. While the intracellular functions of CoA are well-characterized, much less is known about its tissue-specific regulation and systemic physiological roles. Here, using Drosophila melanogaster, we uncover a gut-renal circuit in which dietary VB5 fuels CoA biosynthesis specifically in the Malpighian tubules (MTs, the fly kidney), non-autonomously impacting gut homeostasis. We show that, in the MTs, Myc boosts renal CoA production by directly upregulating the pantothenate kinase Fbl (human PANK1-3 ortholog) and downregulating CG5828, which we characterize as the functional ortholog of the metabolite phosphatase and CoA synthesis suppressor PANK4 (dPANK4). 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.

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Miao, T., Liu, Y., Qadiri, M., Asara, J. M., Hu, Y., Sun, X., Dibble, C., Perrimon, N.. 2025-08-11. Renal Coenzyme A (CoA) Production Fuels Stem Cell Proliferation and Tumor Growth. https://doi.org/10.1101/2025.08.08.669325

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