Discovery of sterol lipid transport proteins and their role in Target of Rapamycin signaling in Saccharomyces cerevisiae cells

• Main Author: Murley, Andrew Christian
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2016
• Subjects: Biochemistry; Cellular biology
• ISBN: 1369615426; 9781369615425

Organelle contact sites are regions where the membranes of two organelles are actively apposed at a distance of 10-30 nm by tethering proteins. Organelle contact sites are critical for lipid and ion exchange between organelles, such as the endoplasmic reticulum (ER) and mitochondria, and may also serve as “microdomains” that regulate the activity of cell signaling pathways and membrane dynamics. In this dissertation, I first give a brief introduction to contact sites between mitochondria and other organelles. Next, I describe the role of the ER-Mitochondria Encounter Structure (ERMES) in tethering ER and mitochondrial membranes in Saccharomyces cerevisiae and directing the mitochondrial division machinery to replicating mitochondrial DNA. Third, I describe my discovery in S. cerevisiae of evolutionarily conserved and previously uncharacterized sterol transport proteins. We renamed these proteins Lipid Transfer at Contact sites 1-4 (Ltc1-4) and facilitate intermembrane sterol transport at organelle contact sites. Our evidence indicates that through their sterol transfer activity these proteins control the activity of Target of Rapamycin (TOR) signaling. They do this by creating membrane microdomains that regulate the partitioning of key TOR Complex (TORC) 1 and 2 effectors on vacuole and plasma membranes, respectively.