UC Davis

Membrane contact sites (MCSs) are specialized regions in cells where organellarmembranes are tethered together and function in many important biological processes such as signaling, ion transport, lipid transfer, and more. MCSs occur between distinct organelles and the endoplasmic reticulum (ER) is most frequently one of the partner membranes, but they are also observed between two membranes of the same organelle, such as the inner and outer mitochondrial membranes (IMM and OMM, respectively). The work of this thesis explores the functional and molecular features of various contact sites. After a brief introduction to contact sites with an emphasis on ERmitochondria contact sites, I describe an atomic model for how a protein complex can bridge the IMM and OMM. Finally, I show how an evolutionary conserved sterol transporter, Lipid Transfer at Contact site 1 (Ltc1), localizes between ER-mitochondria and ER-vacuole MCSs where it carries out separate functions. My evidence indicates that the distribution of Ltc1 localization – and therefore the ratio of its functional output – is best captured by a difference of affinity for its two protein partners at each organelle.