The molecular mechanism of on-demand sterol biosynthesis at organelle contact sites.
Naama ZungNitya AravindanAngela BoshnakovskaRosario ValentiNoga PremingerFelix JonasGilad YaakovMathilda M WilloughbyBettina HombergJenny KellerMeital KupervaserNili DezorellaTali DadoshSharon G WolfMaxim ItkinSergey MalitskyAlexander BrandisNaama BarkaiRubén Fernández-BusnadiegoAmit R ReddiPeter RehlingDoron RapaportMaya SchuldinerPublished in: bioRxiv : the preprint server for biology (2024)
Contact-sites are specialized zones of proximity between two organelles, essential for organelle communication and coordination. The formation of contacts between the Endoplasmic Reticulum (ER), and other organelles, relies on a unique membrane environment enriched in sterols. However, how these sterol-rich domains are formed and maintained had not been understood. We found that the yeast membrane protein Yet3, the homolog of human BAP31, is localized to multiple ER contact sites. We show that Yet3 interacts with all the enzymes of the post-squalene ergosterol biosynthesis pathway and recruits them to create sterol-rich domains. Increasing sterol levels at ER contacts causes its depletion from the plasma membrane leading to a compensatory reaction and altered cell metabolism. Our data shows that Yet3 provides on-demand sterols at contacts thus shaping organellar structure and function. A molecular understanding of this protein's functions gives new insights into the role of BAP31 in development and pathology.
Keyphrases
- endoplasmic reticulum
- cell wall
- endothelial cells
- estrogen receptor
- binding protein
- palliative care
- electronic health record
- cell therapy
- breast cancer cells
- stem cells
- induced pluripotent stem cells
- saccharomyces cerevisiae
- machine learning
- single molecule
- mesenchymal stem cells
- protein protein
- bone marrow
- deep learning