How to build a contact site? The molecular mechanism of on-demand sterol biosynthesis at organelle contact sites

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• Maya Schuldiner - Weizmann Institute
• Thursday 05 February 2026, 15:00-16:00
• Jean Thomas Lecture theatre, Sanger Building, Tennis Court Road.

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Contact sites are specialized zones of proximity between organelles, essential for communication and coordination. The formation of Endoplasmic Reticulum (ER) contact sites, relies on a unique membrane environment enriched in sterols. However, how these sterol-rich domains are formed and maintained was unclear. We found that the yeast membrane protein Yet3, homolog of human BAP31 , localizes to multiple ER contacts. We show that Yet3 interacts with the post-squalene ergosterol biosynthesis enzymes through its transmembrane domains. Yet3 recruits the enzymes to create sterol-rich environments. Increasing sterols at ER contacts causes their depletion from the plasma membrane, leading to a compensatory reaction and altered cell metabolism. We demonstrate that the molecular function of Yet3 and BAP31 is conserved. Our data shows that Yet3 and BAP31 provide on-demand sterols at contacts thus shaping organellar structure and function. This molecular understanding provides new insights into the role of BAP31 in development and pathology.

This talk is part of the Biochemistry Seminar Series - External Speakers series.

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