Cytoophidium complexes resonate with cell fates

ABSTRACT Metabolism is a fundamental characteristic of life. In 2010, we discovered that the metabolic enzyme CTP synthase (CTPS) can assemble a snake like structure inside cells, which we call the cytoophidium. Including CTPS, an increasing number of metabolic enzymes have been found to form cytoophidia in cells. However, the distribution and relationship among cytoophidia formed by different metabolic enzymes remain elusive. Here we investigate five metabolic enzymes that can form cytoophidia, namely Asn1, Bna5, CTPS (ie. Ura7), Glt1, and Prs5 in Saccharomyces cerevisiae. We find that multiple cytoophidia can be assembled into cytoophidium complexes by docking one after another. Glt1 cytoophidia tend to assemble in non-quiescent cells, while CTPS cytoophidia are more abundant in quiescent cells and form complexes with Prs5 and Asn1 cytoophidia. Blocking CTPS cytoophidium assembly can lead to a non-quiescent phenotype and increase the assembly of Glt1 cytoophidia, Bna5 cytoophidia, and cytoophidium complexes. Blocking CTPS cytoophidium assembly also inhibits the NAD biosynthesis pathway, which includes Bna5 and Sir2. Consistent with this result, the non-quiescent phenotype caused by blocking CTPS cytoophidium assembly can be rescued by blocking Glt1 cytoophidium assembly, supplementing nicotinic acid, or overexpressing Sir2. Our results indicate that the assembly of cytoophidium complexes with different compositions resonates with distinct cell fates. HIGHLIGHTS Multiple cytoophidia can be assembled into cytoophidium complexes by docking one after another. CTPS cytoophidia blockage impedes quiescence and boosts Glt1-Bna5 cytoophidium complex. Glt1 cytoophidium blockage restores quiescence and Bna5 inhibition in NAD pathway. Activating NAD utilizing SIR2 rescues CTPS cytoophidium blockage induced non-quiescence. Competing Interest Statement The authors have declared no competing interest.