Structure and function of Organelle Contact Sites

Abstract

Organelle contactsites are specialized intracellular zones called membrane contact sites (MCS),in which two distinct suborganelles are closely apposed in eukaryotic cells. MCSsplay pivotal roles in cellular processes such as cooperative lipid biosynthesis,ion homeostasis, and interorganellar trafficking of molecules in eukaryoticcells. The MCSs are physically formed through dynamic and direct interactionsbetween proteins that are located in two distinct subcompartments. In thistalk, I will introduce structural and functional studies for two representativeMCSs, nucleus-vacuole contact site and endoplasmic reticulum (ER)-mitochondriacontact site. The nucleus–vacuole junction (NVJ) is the first identifiedinterorganellar MCS in the budding yeast Saccharomycescerevisiae, and its formation depends on the nuclear membrane protein Nvj1pand vacuolar membrane protein Vac8p. Here, I will show the crystal structure ofVac8p–Nvj1p complex. The endoplasmic reticulum–mitochondria encounter structure(ERMES) is a protein complex that plays a tethering role in physicallyconnecting ER and mitochondria membranes. The ERMES complex is composed ofMdm12, Mmm1, and Mdm34, which have a SMP domain in common, and Mdm10. I willshow the crystal structure of S.cerevisiae Mdm12. Based on these structures, I will address the molecularmechanisms by which the protein complexes are organized, mediate the formationof membrane contact sites, and perform their versatile functions at thecircumscribed area.