Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division in Saccharomyces cerevisiae

Abstract

Continuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in Saccharomyces cerevisiae increased the abundance of lipids and promoted nuclear elongation and division. De-repressing translation of acetyl CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in other eukaryotes. In this report, the authors show that increasing lipid synthesis promotes the division of the nucleus in yeast cells, a model eukaryotic organism. They also implicate phosphoinositide signaling in the control of nuclear division. Because lipid metabolic and signaling pathways are highly conserved, it is possible that these activities also control nuclear division in other organisms. AUTHOR SUMMARY In this report, the authors show that increasing lipid synthesis promotes the division of the nucleus in yeast cells, a model eukaryotic organism. They also implicate phosphoinositide signaling in the control of nuclear division. Because lipid metabolic and signaling pathways are highly conserved, it is possible that these activities also control nuclear division in other organisms.

One-carbon metabolic enzymes are regulated during cell division and make distinct contributions to the metabolome and cell cycle progression inSaccharomyces cerevisiae

“…2014). Conversely, we have shown that increased lipogenesis promotes nuclear division (Maitra et al . 2022).…”

“…We had previously reported that increased lipogenesis promotes nuclear elongation and division (Maitra et al . 2022).…”

“…Before metaphase, the nucleus elongates across the bud neck, between the mother cell and the large bud. The ratio of the long:short axes of the nucleus provides a metric of nuclear elongation (Maitra et al .2022). A ratio of one corresponds to a spherical nucleus, while values greater than 1 reflect nuclear elongation.…”

“…In yeast, Cki1p encodes choline kinase, which catalyzes the first step in phosphatidylcholine synthesis in the choline salvage pathway. We previously showed that cki1Δ cells have a slightly smaller critical size in rich, YPD medium (Maitra et al . 2022).…”

“…To visualize the nuclear envelope, we followed the same procedures we described previously (Maitra et al . 2022).…”