Faculty

Robert P. Donaldson
Professor of Biology
Director of the GW Howard Hughes Medical Institute for Undergraduate Education in Computational Molecular Biology
Oxidations in Peroxisomes
Bell 101A
Lab: (202) 994-6931
Office: (202) 994-6094
Fax: (202) 994-6100
E-Mail: robdon@gwu.edu

Courses

• BISC 5 - The Biology of Nutrition and Health
• BISC 14 - Introductory Biology: Cell and Molecules
• BISC 105 - Plant Biochemistry
• BISC 106 - Special Topics in Biochemistry
• BISC 183 - Biology of Proteins
• BMSC 210 - Biomedical Science Core: Macromolecular Interactions – Proteins (Course Bulletin not up yet)
• CS 177 - Introduction to Bioinformatics
• Computational Molecular Biology Workshop

Education

B.A., Biology, University of Texas, 1964
M.S., Botany, Miami University, OH, 1966
Ph.D., Biochemistry, Michigan State University, MI, 1971

Research

Peroxisomes are subcellular compartments that house oxidations that produce hydrogen peroxide. This occurs in most eukaryotic organisms including yeasts, plants and animals. Peroxisomes in yeast allow them to metabolize hydrocarbons and methanol. Their two main functions in plants are photorespiration in leaves and the conversion of oils to sugars in germinating seeds. In humans peroxisomes are responsible for the oxidation of certain dietary hydrocarbons and several human diseases result from genetic defects in peroxisomal function. We are investigating the consequences of the oxidative processes that occur in peroxisomes, using germinating castor bean (Ricinus communis) as a model system for our biochemical studies.

The oxidation of fatty acids in peroxisomes creates superoxide and hydroxyl radicals as well as hydrogen peroxide. All of these Reactive Oxygen Species (ROS) can damage proteins and nucleic acids in cells. This damage is prevented to some extent by enzymes within peroxisomes such as superoxide dismutase, catalase, ascorbate peroxidase, and thioredoxin peroxidase that scavenge and detoxify the ROS. Graduate students in the laboratory have been investigating the protective functions of some of these enzymes. For example, Tulin Olcum-Yanik, who completed her PhD in 2002, investigated the idea that catalase is physically associated with another protein that is contained in peroxisomes in a way that shields that protein from oxidative damage by hydrogen peroxide. Dina Karyotou’s PhD project concerned ascorbate peroxidase that is associated with the peroxisomal membrane and can scavenge smaller concentrations of hydrogen peroxide than catalase. This peroxidase is situated to prevent the escape of hydrogen peroxide from the peroxisome.

Currently, Mimi Kwak an MS student and Thy Nguyen an undergraduate are working on the oxidative damage of proteins within peroxisomes. We have devised ways to detect the extent of oxidation of individual proteins and to determine how this damage affects the functions of the proteins. The hypothesis under consideration is that proteins contained within peroxisomes are resistant to oxidation and retain functions despite oxidative damage. Protein oxidation is of broad significance in biology because it is thought to be one of the main consequences of aging. Thus, controlling oxidation can prolong the life and health of an organism.

Publications

Nguyen A.T., Donaldson R.P. 2005 Metal-catalyzed oxidation induces carbonylation of peroxisomal proteins and loss of enzymatic activities. Arch Biochem Biophys. 2005 Jul 1;439(1):25-31.

Yanik T., Donaldson R.P. 2005 A protective association between catalase and isocitrate lyase in peroxisomes. Arch Biochem Biophys. 435(2):243-52.

Karyotou K., Donaldson R.P. 2005 Ascorbate peroxidase, a scavenger of hydrogen peroxide in glyoxysomal membranes. Arch Biochem Biophys. Feb 15;434(2):248-57.

Donaldson R.P. 2002 Peroxisomal membrane proteins. In A Baker and IA Grahm, eds, Plant peroxisomes, Kluwer Academic Publishers, Dordrecht, pp 259-278.
www.wkap.nl/prod/b/1-4020-0587-3

Donaldson R.P., Karyotou K., Assadi M., Olcum T. 2000. Peroxisomes and glyoxysomes in plants. Encyclopedia of Life Sciences. Internet publication of Nature/McMillan Press.
www.naturereference.com/els

Wolins N.E., Donaldson R.P. 1997 Binding of the peroxisomal protein targeting sequence SKL is specified by a low-affinity site in castor bean glyoxysomal membranes. A domain next to the SKL binds to a high-affinity site. Plant Physiol. 113:943-949.
www.plantphysiol.org/cgi/reprint/113/3/943.pdf

Del Rio L.A., Donaldson R.P. 1995 Production of superoxide radicals in glyoxysomal membranes from castor bean endosperm. J. Plant Physiol. 146:283-287

Wolins N.E., Donaldson R.P. 1994 Specific binding of the peroxisomal protein targeting sequence to glyoxysomal membranes. J. Biol. Chem. 269: 1149-1153
www.jbc.org/cgi/reprint/269/2/1149.pdf

Donaldson R.P., Luster D.G. 1991 Multiple forms of plant cytochromes P-450.Plant Physiol. 96:669-674.

Alani A.A., Luster D.G., Donaldson, R.P. 1991 Development of ER and glyoxysomal membrane redox activities during castor bean germination. Plant Physiol. 94: 1842-1848.

Lyons H.T., Kharroubi A.., Wolins N., Tenner S., Chanderbhan R.F., Fiskum G., Donaldson R.P. 1991. Elevated cholesterol and decreased sterol carrier protein-2 in peroxisomes from AS-30D hepatoma compared to normal rat liver. Arch. Biochem. Biophys. 285: 238-245.

Bowditch M.I., Donaldson R.P. 1990. Ascorbate free radical reduction by glyoxysomal membranes. Plant Physiol 94; 531-537

Mangurian L.P., R.P. Donaldson 1989 Development of peroxisomal beta-oxidation enzymes in brown adipose tissue of perinatal rabbits. Biology of the Neonate 57:349-357.