Import of proteins across the peroxisomal membrane.
We have previously demonstrated that gold particles, bearing the peroxisomal targeting sequence can be imported into peroxisomes following microinjection into mammalian cells. Early time points, show 5-9 nm gold-SKL particles in association with the concave face of membrane loops that appear to close into vesicles. We hypothesize that autophagy is a method by which proteins can enter the peroxisomal matrix. This method would allow the import of a stably folded or multimeric protein across the peroxisomal membrane. Cell lines derived from Zellweger patients of various complementation groups will be used to study the effects of the loss of function of a single gene-product on the process of import. The use of such lines may yield important results concerning the nature of peroxisomal biogenesis and protein import into this organelle.
Effects of aging on peroxisomal protein import.
Peroxisomes produce hydrogen peroxide as a product of their oxidative enzymes, and possess the antioxidant enzyme catalase to decompose this damaging compound. We have demonstrated that import of catalase into the peroxisomal matrix is reduced as cells age. My lab and the laboratories of my collaborators are studying whether a decrease in catalase contributes to cellular aging. In addition, we are studying the effects of restoring catalase to the peroxisome on free-radical levels, peroxisome and cellular functions, and aging and longevity in animal models
• Walton, P.A. and Pizzitelli, M. (2012) Effects of peroxisomal catalase inhibition on mitochondrial function. Frontiers in Integrative Physiology 3, 108-117.
• Koepke, J.I., Wood, C.S., Terlecky, L.J., Walton, P.A. and Terlecky, S.R. (2008) Progeric effects of catalase inactivation in human cells. Toxicology and Applied Pharmacology 232: 99-108.
• Koepke, J.I., Nakrieko, K.A., Wood, C.S., Boucher, K.K., Terlecky, L.J., Walton, P.A. and Terlecky, S.R. (2007) Restoration of peroxisomal catalase import in a model of human cellular aging. Traffic 8: 1590-1600.
• Terlecky, S.R., Koepke, J.I., and Walton, P.A. (2006) Peroxisomes and Aging. Biochim. Biophys. Acta-Molec. Cell Res. 1763: 1749-1754.
• Wood, C.S., Koepke, J.I., Teng, H., Boucher, K.K., Chang, P., Katz, S., Terlecky, L.J., Papanayotou, I., Walton, P.A. and Terlecky, S.R. (2006) Hypocatalasemic fibroblasts accumulate hydrogen peroxide and display age-related pathologies. Traffic 7: 1-11.
• Brocard, C.B., Boucher, K., Jedeszko, C., Kim, P. and Walton, P.A. (2005) Requirement for microtubules and dynein-motors in the earliest stages of peroxisome biogenesis. Traffic 6: 386-395 (includes cover illustration)
• Terlecky, S.R. and Walton, P.A. (2004) The Cell Biology and Biogenesis of Peroxisomes in Human Health and Disease. In: The Biogenesis of Cellular Organelles . Mullins, C., editor, Landes Bioscience Publishing Company, Georgetown, Texas.
• Brocard, C.B., Jedeszko, C., Song, H.C., Terlecky, S.R. and Walton, P.A. (2003) Protein structure and import into the peroxisomal matrix. Traffic 4: 74-82
• Legakis, J.E., Koepke, J.I., Jedeszko, C., Barlaskar, B., Terlecky, L.J., Edwards, H.J., Walton, P.A. and Terlecky, S.R. (2002) Peroxisome senescence in human fibroblasts. Molec. Biol. Cell 13: 4243-4255 (includes cover illustration)
• Walton, P.A., Hill, P.E., and Subramani, S. (1995) Import of stably-folded proteins into peroxisomes. Molec. Biol. Cell 6: 675-683.