William Abraham Prinz, Ph.D.
Lipid Trafficking and Organelle Biogenesis Section, Laboratory of Cell and Molecular Biology
Building 8, Room 301
8 Center Dr
Bethesda, MD 20814
+1 301 451 4592
The ultimate purpose of our research is to understand how cells regulate the shape and lipid composition of membranes to optimize organelle function.
My lab studies organelle biogenesis in the model organism S. cerevisiae with a combination of biochemical, genetic, and imaging approaches. Three projects in my lab include the following.
Intracellular lipid trafficking
We are working to identify proteins required for nonvesicular lipid trafficking in cells and to understand their role in organelle biogenesis and lipid metabolism. Previously, we focused on the role of oxysterol-binding protein homologs in sterol trafficking. More recently, we began studying phospholipid exchange between the endoplasmic reticulum (ER) and mitochondria and the role of close contacts between these organelles in lipid trafficking.
The ER forms a large, dynamic network that extends throughout the cell, with tubular and sheet-like domains. The reticulons and reticulon-like proteins help maintain this structure by stabilizing tubules and the edges of sheets. We are working to understand how these proteins shape the ER and what proteins they work in concert with. In addition, we are working to define the relationship between ER shape and ER function. For example, we recently found that ER-shaping proteins play a role in lipid exchange between the ER and mitochondria, perhaps by maintaining the shape of the ER at regions where these organelles come in close contact. In a second project, we are studying the role of the dynamin-like protein Sey1 in ER-ER fusion and lipid metabolism.
Formation and function of organelle contact sites
There is growing evidence that regions of close contact between organelles, often called membrane contact sites, are places where signals and small molecules are exchanged. Often, contact is between the ER and a second organelle. We are studying contacts between the ER and mitochondria, the plasma membrane, the Golgi complex, and the vacuole to understand how these sites form and what role they play in intra-organelle lipid transport and lipid metabolism.
Applying our Research
Defects in lipid metabolism and organelle biogenesis are associated with numerous diseases. Gaining insight into the basic processes in cells will help us understand how defects in them contribute to human disease.
Need for Further Study
Researchers have yet to study how the sizes of organelles are determined.
- Ph.D., Harvard University, 1996
Choudhary V, Golani G, Joshi AS, Cottier S, Schneiter R, Prinz WA, Kozlov MM. Architecture of Lipid Droplets in Endoplasmic Reticulum Is Determined by Phospholipid Intrinsic Curvature. Curr Biol. 2018;28(6):915-926.e9.
Joshi AS, Nebenfuehr B, Choudhary V, Satpute-Krishnan P, Levine TP, Golden A, Prinz WA. Lipid droplet and peroxisome biogenesis occur at the same ER subdomains. Nat Commun. 2018;9(1):2940.
Liu LK, Choudhary V, Toulmay A, Prinz WA. An inducible ER-Golgi tether facilitates ceramide transport to alleviate lipotoxicity. J Cell Biol. 2017;216(1):131-147.
Joshi AS, Huang X, Choudhary V, Levine TP, Hu J, Prinz WA. A family of membrane-shaping proteins at ER subdomains regulates pre-peroxisomal vesicle biogenesis. J Cell Biol. 2016;215(4):515-529.
Toulmay A, Prinz WA. Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells. J Cell Biol. 2013;202(1):35-44.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on November 19th, 2019