Intracellular Lipid Trafficking and Organelle Biogenesis

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

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. We have found that lipid synthesis at contacts between the ER and mitochondria (and other contact sites) promotes lipid exchange and are working to discover the mechanism. We are also working on the role of a novel family of lipid transport proteins in lipid exchange between the ER and mitochondria. These studies are primarily in the yeast S. cerevisiae, but family of proteins is conserved in humans and we will study these proteins as well. In a second project, we are working on a group of proteins that are structurally related to Vps13, a lipid transfer protein that may facilitate lipid transfer by allowing lipids to slide betweeen membranes in a hydrophoblic groove that runs the length of the protein. One of the proteins we are working on is necessary to bring phosphatidylethanolamine to the ER to support the synthesis of GPI anchors. A third project focuses on understanding how cell prevent the accumulation of lipid peroxides . We have initiated a high throughput, transposon-based screen to identify proteins required for cells to survive exposure to lipid peroxides.