Coenzyme A precursors flow from mother to zygote and from microbiome to host

Yi Yu, Marianne van der Zwaag, Jouke Jan Wedman, Hjalmar Permentier, Niels Plomp, Xiu Jia, Bart Kanon, Ellie Eggens-Meijer, Girbe Buist, Hermie Harmsen, Jan Kok, Joana Falcao Salles, Bregje Wertheim, Susan J. Hayflick, Erick Strauss, Nicola A. Grzeschik, Hein Schepers, Ody C.M. Sibon

Research output: Contribution to journalArticlepeer-review

Abstract

Coenzyme A (CoA) is essential for metabolism and protein acetylation. Current knowledge holds that each cell obtains CoA exclusively through biosynthesis via the canonical five-step pathway, starting with pantothenate uptake. However, recent studies have suggested the presence of additional CoA-generating mechanisms, indicating a more complex system for CoA homeostasis. Here, we uncovered pathways for CoA generation through inter-organismal flows of CoA precursors. Using traceable compounds and fruit flies with a genetic block in CoA biosynthesis, we demonstrate that progeny survive embryonal and early larval development by obtaining CoA precursors from maternal sources. Later in life, the microbiome can provide the essential CoA building blocks to the host, enabling continuation of normal development. A flow of stable, long-lasting CoA precursors between living organisms is revealed. This indicates the presence of complex strategies to maintain CoA homeostasis.

Original languageEnglish (US)
Pages (from-to)2650-2665.e12
JournalMolecular Cell
Volume82
Issue number14
DOIs
StatePublished - Jul 21 2022

Keywords

  • Drosophila
  • PKAN
  • acetyl-CoA
  • coenzyme A
  • maternal contribution
  • metabolism
  • microbiome
  • pantetheine
  • pantothenate kinase
  • vitamin B5

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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