The transfer of phospholipids between the ER and mitochondria is critical for mitochondrial biogenesis. Mitochondria cannot synthesize many of the lipids they require for membrane biogenesis and yet there is little or no vesicular trafficking to mitochondria. It is thought that lipids are transferred from the ER to mitochondria by a poorly understood nonvesicular mechanism. This transport has been proposed to occur at regions where the ER and mitochondria are closely apposed. In order to identify proteins required for phospholipids exchange between the ER and mitochondria we performed a genetic screen in collaboration with Dr. Chistopher Loewen at the University of British Columbia. We identified a conserved complex of ER proteins. We measured the exchange of phosphatidylserine between the ER and mitochondria in mutants missing a number of components of this complex. We found that lipid exchange slowed about 5 fold both in vivo and in vitro. This work is being prepared for submission. In a second project, we are studying the role of close contacts between the ER and plasma membrane in lipid exchange between these organelles. We have generated a yeast strain in which these contacts are almost completely abolished by removing 6 of the 7 proteins needed to maintain them. We have a conditional mutation in the seventh protein and in restrictive conditions the strain is not viable. We are using this strain to determine the role of contacts between the ER and plasma membrane in sterol and phosphatidylserine exchange between these organelles. A third project focuses on the formation and function of raft-like lipid domains that we found form in the yeast vacuole (the equivalent of lysosomes in higher eukaryotes) in response to stress. We are investigating both the formation of these domains and what role they play in stress.

Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
2013
Total Cost
$543,673
Indirect Cost
City
State
Country
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Prinz, William A (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205:759-69
Toulmay, Alexandre; Prinz, William A (2013) Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells. J Cell Biol 202:35-44
Prinz, William A (2013) A bridge to understanding lipid droplet growth. Dev Cell 24:335-6
Tavassoli, Shabnam; Chao, Jesse T; Young, Barry P et al. (2013) Plasma membrane--endoplasmic reticulum contact sites regulate phosphatidylcholine synthesis. EMBO Rep 14:434-40
Muthusamy, Baby-Periyanayaki; Raychaudhuri, Sumana; Natarajan, Paramasivam et al. (2009) Control of protein and sterol trafficking by antagonistic activities of a type IV P-type ATPase and oxysterol binding protein homologue. Mol Biol Cell 20:2920-31
Raychaudhuri, Sumana; Prinz, William A (2008) Nonvesicular phospholipid transfer between peroxisomes and the endoplasmic reticulum. Proc Natl Acad Sci U S A 105:15785-90
Canagarajah, Bertram J; Hummer, Gerhard; Prinz, William A et al. (2008) Dynamics of cholesterol exchange in the oxysterol binding protein family. J Mol Biol 378:737-48