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
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Zip Code
Choudhary, Vineet; Golani, Gonen; Joshi, Amit S et al. (2018) Architecture of Lipid Droplets in Endoplasmic Reticulum Is Determined by Phospholipid Intrinsic Curvature. Curr Biol 28:915-926.e9
Lin, Cheng-Chao; Kurashige, Mahiro; Liu, Yi et al. (2018) A cleavage product of Polycystin-1 is a mitochondrial matrix protein that affects mitochondria morphology and function when heterologously expressed. Sci Rep 8:2743
Friedman, Jonathan R; Kannan, Muthukumar; Toulmay, Alexandre et al. (2018) Lipid Homeostasis Is Maintained by Dual Targeting of the Mitochondrial PE Biosynthesis Enzyme to the ER. Dev Cell 44:261-270.e6
Hayes, Matthew; Choudhary, Vineet; Ojha, Namrata et al. (2017) Fat storage-inducing transmembrane (FIT or FITM) proteins are related to lipid phosphatase/phosphotransferase enzymes. Microb Cell 5:88-103
Liu, Li-Ka; Choudhary, Vineet; Toulmay, Alexandre et al. (2017) An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. J Cell Biol 216:131-147
Michaud, Morgane; Prinz, William A; Jouhet, Juliette (2017) Glycerolipid synthesis and lipid trafficking in plant mitochondria. FEBS J 284:376-390
Prinz, William A (2017) A cholesterol-sensing mechanism unfolds. J Biol Chem 292:19974-19975
Kannan, Muthukumar; Lahiri, Sujoy; Liu, Li-Ka et al. (2017) Phosphatidylserine synthesis at membrane contact sites promotes its transport out of the ER. J Lipid Res 58:553-562
Murley, Andrew; Yamada, Justin; Niles, Bradley J et al. (2017) Sterol transporters at membrane contact sites regulate TORC1 and TORC2 signaling. J Cell Biol 216:2679-2689
Michaud, Morgane; Gros, Valérie; Tardif, Marianne et al. (2016) AtMic60 Is Involved in Plant Mitochondria Lipid Trafficking and Is Part of a Large Complex. Curr Biol 26:627-39

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