Abstract #51

An intraperoxisomal signaling cascade initiates peroxisome division by triggering the stepwise remodeling of lipid and protein composition of the peroxisomal membrane. Christopher Gregg, Tong Guo, Tatiana Boukh-Viner, Alexander Goldberg, Simon Bourque, Pavlo Kyryakov, Farhana Banu, Karen Hung Yeung San, Cristina Sison, Jonathan Solomon, Vivianne Wong, Oleh Petriv, Vladimir Titorenko. Biology Department, Concordia University, Montreal, Quebec, Canada.
   We have identified an unusual mechanism regulating organelle division. Yeast peroxisomes do not grow and divide at the same time. The growth of immature peroxisomal vesicles, which is accomplished by the stepwise import of matrix proteins, and their development into mature peroxisomes occur before completely assembled mature peroxisomes undergo division. The division of immature peroxisomal vesicles is negatively regulated by Pex16p, a protein that binds lysophosphosphatidic acid (LPA) in the inner membrane leaflet of these vesicles. The binding of Pex16p to LPA prevents the formation of diacylglycerol (DAG), a particularly potent inducer of negative curvature and membrane bending, in a membrane-associated biosynthetic pathway. The stepwise import of distinct subsets of matrix proteins into different immature intermediates along the peroxisome assembly pathway causes the redistribution of a peroxisomal protein, acyl-CoA oxidase (Aox), from the matrix to the membrane. A significant redistribution of Aox occurs only in mature peroxisomes. Inside mature peroxisomes, Aox interacts with Pex16p. This interaction between Aox and Pex16p greatly decreases the affinity between Pex16p and LPA, thereby allowing LPA to enter the biosynthetic pathway leading to the formation of DAG in the inner membrane leaflet. The subsequent spontaneous movement of DAG into the outer leaflet promotes the reorganization of the bilayer configuration of the membrane and recruits the dynamin-like GTPase Vps1p to the cytosolic face of the peroxisome. A complex between a distinct set of peroxisomal membrane proteins, Vps1p, and several actin cytoskeletal proteins is then assembled on the peroxisomal surface. This protein team promotes membrane scission and fission, executing the terminal steps of peroxisome division.

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