Peroxisomes are metabolic compartments that are essential for human and plant development. Although understanding of how matrix proteins are imported into peroxisomes is increasing, mechanisms for turning over damaged or obsolete peroxisomal proteins remain largely obscure. The proposed studies will address peroxisome-associated protein degradation in Arabidopsis thaliana;the unique peroxisomal functions and facile genetics of this system will allow dissection of peroxisomal processes in an intact organism. Peroxins, encoded by PEX genes, are necessary for peroxisome biogenesis. Most peroxins act in matrix protein import;this work will determine whether a subset of these peroxins have additional roles in matrix protein turnover. Preliminary data suggest that a subset of peroxins work together both in receptor recycling and in a novel type of retrotranslocation - the removal for degradation of peroxisomal matrix proteins that are damaged or no longer needed.
Three specific aims are proposed to identify components and molecular requirements of peroxisome-associated protein degradation.
Aim 1 will characterize matrix protein localization and stability in mutants defective in peroxins and proteasome subunits.
Aim 2 will identify cis-acting molecular signals necessary for degradation of two peroxisomal matrix proteins that undergo regulated destruction during a specific stage of seedling development.
Aim 3 will recover mutants defective in known and undiscovered components of the peroxisome-associated degradation machinery. The successful completion of these aims will begin to address an unsolved mystery of peroxisome biology: How do peroxisomes dispose of damaged or obsolete proteins? Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal in infancy and are characterized by severe mental retardation, neuronal migration defects, craniofacial abnormalities, and other symptoms. 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. Adding an evolutionarily distinct model to the study of peroxisome biology will allow the development of model and hypotheses to expand and refine our understanding of these essential organelles.

Public Health Relevance

Using Arabidopsis to Uncover New Roles for Peroxins Peroxisomes are subcellular compartments housing critical metabolic reactions and are essential for normal human development. Peroxisomal defects underlie a group of inherited syndromes known as peroxisome biogenesis disorders, which are generally fatal early in infancy. The proposed experiments will elucidate how cells dispose of proteins within peroxisomes when they are damaged or no longer needed.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM079177-04
Application #
8215748
Study Section
Membrane Biology and Protein Processing (MBPP)
Program Officer
Ainsztein, Alexandra M
Project Start
2009-03-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2014-02-28
Support Year
4
Fiscal Year
2012
Total Cost
$282,985
Indirect Cost
$91,865
Name
Rice University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
050299031
City
Houston
State
TX
Country
United States
Zip Code
77005
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
Rinaldi, Mauro A; Patel, Ashish B; Park, Jaeseok et al. (2016) The Roles of β-oxidation and Cofactor Homeostasis in Peroxisome Distribution and Function in Arabidopsis thaliana. Genetics :
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
Burkhart, Sarah E; Kao, Yun-Ting; Bartel, Bonnie (2014) Peroxisomal ubiquitin-protein ligases peroxin2 and peroxin10 have distinct but synergistic roles in matrix protein import and peroxin5 retrotranslocation in Arabidopsis. Plant Physiol 166:1329-44
Bartel, Bonnie; Farmer, Lisa M; Rinaldi, Mauro A et al. (2014) Mutation of the Arabidopsis LON2 peroxisomal protease enhances pexophagy. Autophagy 10:518-9
Burkhart, Sarah E; Lingard, Matthew J; Bartel, Bonnie (2013) Genetic dissection of peroxisome-associated matrix protein degradation in Arabidopsis thaliana. Genetics 193:125-41
Farmer, Lisa M; Rinaldi, Mauro A; Young, Pierce G et al. (2013) Disrupting autophagy restores peroxisome function to an Arabidopsis lon2 mutant and reveals a role for the LON2 protease in peroxisomal matrix protein degradation. Plant Cell 25:4085-100
Hu, Jianping; Baker, Alison; Bartel, Bonnie et al. (2012) Plant peroxisomes: biogenesis and function. Plant Cell 24:2279-303

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