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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Membrane Biology and Protein Processing Study Section (MBPP)
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Ainsztein, Alexandra M
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Rice University
Schools of Arts and Sciences
United States
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Woodward, Andrew W; Bartel, Bonnie (2018) Biology in Bloom: A Primer on the Arabidopsis thaliana Model System. Genetics 208:1337-1349
Kao, Yun-Ting; Gonzalez, Kim L; Bartel, Bonnie (2018) Peroxisome Function, Biogenesis, and Dynamics in Plants. Plant Physiol 176:162-177
Gonzalez, Kim L; Ratzel, Sarah E; Burks, Kendall H et al. (2018) A pex1 missense mutation improves peroxisome function in a subset of Arabidopsis pex6 mutants without restoring PEX5 recycling. Proc Natl Acad Sci U S A 115:E3163-E3172
Rinaldi, Mauro A; Fleming, Wendell A; Gonzalez, Kim L et al. (2017) The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology. Plant Physiol 174:2231-2247
Gonzalez, Kim L; Fleming, Wendell A; Kao, Yun-Ting et al. (2017) Disparate peroxisome-related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization. Plant J 92:110-128
Rinaldi, Mauro A; Patel, Ashish B; Park, Jaeseok et al. (2016) The Roles of ?-Oxidation and Cofactor Homeostasis in Peroxisome Distribution and Function in Arabidopsis thaliana. Genetics 204:1089-1115
Reumann, Sigrun; Bartel, Bonnie (2016) Plant peroxisomes: recent discoveries in functional complexity, organelle homeostasis, and morphological dynamics. Curr Opin Plant Biol 34:17-26
Young, Pierce G; Bartel, Bonnie (2016) Pexophagy and peroxisomal protein turnover in plants. Biochim Biophys Acta 1863:999-1005
Kao, Yun-Ting; Fleming, Wendell A; Ventura, Meredith J et al. (2016) Genetic Interactions between PEROXIN12 and Other Peroxisome-Associated Ubiquitination Components. Plant Physiol 172:1643-1656
Kao, Yun-Ting; Bartel, Bonnie (2015) Elevated growth temperature decreases levels of the PEX5 peroxisome-targeting signal receptor and ameliorates defects of Arabidopsis mutants with an impaired PEX4 ubiquitin-conjugating enzyme. BMC Plant Biol 15:224

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