Peroxisomes are eukaryotic organelles that sequester various oxidative reactions, thereby protecting cytosolic constituents from oxidative damage. Although understanding of the biological consequences of peroxisome function and dysfunction is increasing, diverse and effective chemicals that modulate peroxisome biogenesis or activity are not available. The proposed studies will identify and characterize chemical and genetic peroxisome modulators in the model plant Arabidopsis thaliana;the peroxisomal functions, small size, and facile genetics of this organism allow straightforward perturbation and enhancement of peroxisomal processes in a multicellular organism. The experiments proposed in Aim 1 will identify and characterize small molecules that reduce peroxisome function in wild type.
Aim 2 will identify and characterize small molecules that improve peroxisome function in peroxisome-defective mutants. Finally, Aim 3 will identify and characterize modifier mutations that improve peroxisome function in peroxisome-defective mutants. The successful completion of these aims will identify chemicals and molecular alterations that specifically modulate peroxisome biogenesis or peroxisomal protein import, providing new molecular tools and understanding with which to elucidate and modulate peroxisome biogenesis and function not only in plants, but also in other eukaryotes. Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal in infancy or childhood and are characterized by diverse symptoms including mental retardation, neuronal migration defects, and craniofacial abnormalities. The proposed experiments will exploit unique aspects of plant peroxisomes while taking advantage of knowledge from fungal and mammalian systems to provide insights that are likely to apply throughout eukaryotes. Continuing to develop evolutionarily distinct model systems with which to study peroxisome biology will allow advancement of hypotheses and mechanistic models to expand and refine our understanding of these essential organelles.

Public Health Relevance

Peroxisomes are subcellular compartments housing critical metabolic reactions and are essential for normal human and plant development. Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which often are fatal in infancy. The proposed experiments will identify and characterize chemical and genetic modifiers that improve peroxisome functioning in peroxisome-defective mutants.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01GM079177-05
Application #
8760719
Study Section
Membrane Biology and Protein Processing Study Section (MBPP)
Program Officer
Ainsztein, Alexandra M
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Rice University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77005
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