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.