ArticleScience advances2025
Structural dissection of ergosterol metabolism reveals a pathway optimized for membrane phase separation.
Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Ether linkages in phospholipids provide modular control of membrane mechanics.bioRxiv : the preprint server for biology · 2026Article
- Ergosterol from Yeasts PromotesInternational journal of molecular sciences · 2026Article
- Micafungin exposure drives multidrug resistance inbioRxiv : the preprint server for biology · 2026Article
- Macrophage signaling and function are regulated by distinct sterol biochemistries.Journal of lipid research · 2026Article
- Active regulation of intrinsic curvature by eukaryotic phospholipid metabolism.Cell reports. Physical science · 2026Article
- Transport of sphingolipids by yeast Npc2 supports phase separation of the vacuole membrane.The Journal of biological chemistry · 2026Article
- Coupling between sterol and sphingolipid structure in ordered membrane domains.bioRxiv : the preprint server for biology · 2026Article
- Para-dichlorobenzene inhibits Fusarium oxysporum f. sp. cubense tropical race 4 by inducing membrane damage, mitochondrial dysfunction, and transcriptional reprogramming.BMC microbiology · 2026Article
- Transport of sphingolipids by yeast Npc2 supports phase separation of the vacuole membrane.bioRxiv : the preprint server for biology · 2025Article
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Abstract
Sterols are among the most abundant lipids in eukaryotic cells yet are synthesized through notoriously long metabolic pathways. It has been proposed that the molecular evolution of such pathways must have required each step to increase the capacity of its product to condense and order phospholipids. Here, we carry out a systematic analysis of the ergosterol pathway that leverages the yeast vacuole's capacity to phase separate into ordered membrane domains. In the post-synthetic steps specific to ergosterol biosynthesis, we find that successive modifications act to oscillate ordering capacity, settling on a level that supports phase separation while retaining fluidity of the resulting domains. Simulations carried out with each intermediate showed how conformers in the sterol's alkyl tail are capable of modulating long-range ordering of phospholipids, which could underlie changes in phase behavior. Our results indicate that the complexity of sterol metabolism could have resulted from the need to balance lipid interactions required for membrane organization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.