Peroxisomes compartmentalize various metabolic reactions in eukaryotes, thereby protecting the cytosol from oxidative damage. Peroxisomes are essential for life in humans and plants, so partial loss-of-function alleles are necessary to query peroxisome functions. Our finding that conversion of the auxin precursor indole-3-butyric acid (IBA) to the active auxin indole-3-acetic acid (IAA) occurs in peroxisomes motivated our study of the biogenesis, function, and degradation this vital and dynamic organelle.
We employ forward-genetic screens to isolate mutants defective in enzymes catalyzing IBA-to-IAA conversion and mutants defective in biogenesis of peroxisomes, which house these enzymes. Our analysis of these mutants has revealed a new auxin biosynthetic pathway, unanticipated interdependencies among peroxisome biogenesis factors, a novel pathway for degrading peroxisome matrix proteins during developmentally controlled organelle remodeling, and the process of peroxisome degradation via specialized autophagy (pexophagy). We have uncovered multiple intriguing examples in which Arabidopsis peroxisomes more closely resemble mammalian peroxisomes than do yeast or nematode peroxisomes, suggesting that our studies may provide unique insights into human peroxisome biogenesis disorders.
Our current research is using forward genetic, chemical genetic, and cell biological approaches to identify how plant peroxisomes are built, maintained, and degraded in response to developmental needs and environmental challenges. We also are exploring peroxisome interactions with other organelles, such as lipid droplets and the endoplasmic reticulum.
Our peroxin publications
Our pexophagy publications
Our IBA publications
Our peroxisome-related review articles
Matrix protein import. The pex12-1 mutant fails to efficiently import GFP-PTS1 into peroxisomes, visualized in cotyledon epidermal cells.
We are grateful for support
for this research from the NIH (R01GM079177, R35GM130338), the NSF
(IBN-0315596; MCB-0745122, MCB-1516966), and the Robert A. Welch Foundation (C-1309).
Peroxisome biogenesis. Peroxisome biogenesis requires a core set of conserved peroxins (numbered ovals) to import matrix proteins, which are synthesized in the cytosol and targeted to the peroxisome via PEX5 interaction with a C-terminal PTS1 (black proteins) or PEX7 interaction with an N-terminal PTS2 (gray proteins). PEX5 docks with a PEX13-PEX14 complex for cargo delivery; PEX7 binding to PEX5 (in plants and mammals) is required for PTS2-protein delivery. Receptor-recycling peroxins remove PEX5 via mono-ubiquitination by the PEX4 Ub-conjugating enzyme and the PEX12 RING peroxin, allowing removal by the PEX1-PEX6 ATPase complex. PEX5 is poly-ubiquitinated and degraded by the proteasome when recycling is slowed. DEG15 clips the PTS2 signal after matrix protein import.
Autophagy of peroxisomes. When the LON2 peroxisomal protease is dysfunctional, peroxisomes are degraded via autophagy and GFP-PTS1 (green) that is peroxisomal in young seedlings becomes cytosolic as seedlings age. Chlorophyll autofluorescence is in magenta.