Research Summary

My long-term research interest is in membrane biochemistry. Over the years, I have studied the molecular organization of the human red cell membrane and several aspects of the cell biology of the ameba, Dictyostelium discoideum. In addition, the disposition of cell cholesterol has been a recurrent focus. We are currently investigating cellular cholesterol homeostasis: how cells sense their need for this essential plasma membrane lipid and make appropriate adjustments to keep it in balance. We suggest that cells gauge the magnitude of the bulk pool of cholesterol in the plasma membrane by sensing the high activity of the cholesterol in excess of phospholipids. This active excess sets the size of the sterol pool in the endoplasmic reticulum and mitochondria through the flow of cholesterol between the cell surface and intracellular membranes. The endoplasmic reticulum pool then sets the level of activity of several regulatory elements in its membrane that mediate sterol homeostasis while the mitochondria convert cholesterol to oxysterols that serve as messengers of cholesterol excess. The elements of this cholesterol sensing system and how it can be manipulated are under investigation.

Selected Publications

Lange, Y., and Steck, T.L. (2008). Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol. Prog Lipid Res 47, 319-332. (PubMed)

Lange, Y., Ory, D.S., Ye, J., Lanier, M.H., Hsu, F.-F., and Steck, T.L. (2008). Effectors of Rapid Homeostatic Responses of Endoplasmic Reticulum Cholesterol and 3-Hydroxy-3-methylglutaryl-CoA Reductase. J Biol Chem 283, 1445-1455. (PubMed)

Ratajczak, M.K., Ko, Y.T.C., Lange, Y., Steck, T.L., and Lee, K.Y.C. (2007). Cholesterol Displacement from Membrane Phospholipids by Hexadecanol. Biophys J 93, 2038-2047. (PubMed)

Lange Y, Ye J, Steck TL. (2007). Scrambling of phospholipids activates red cell membrane cholesterol. Biochemistry. 46(8):2233-8. Epub 2007 Feb 2. (PubMed)

Lange, Y., J. Ye, and T.L. Steck (2005). Activation of membrane cholesterol by displacement from phospholipids. J Biol Chem. 280:36126-31. (PubMed)

Lange Y, Ye J, Steck TL. (2004). How cholesterol homeostasis is regulated by plasma membrane cholesterol in excess of phospholipids. Proc Natl Acad Sci USA. 101,1664-11667. (PubMed)

Steck, T.L., Ye, J., and Lange, Y. (2002). Probing red cell membrane cholesterol movement with cyclodextrin. Biophys. J., 83, 2118-2125. (PubMed)