# Using suppressor analysis to elucidate peroxisome biogenesis and peroxin function

> **NIH NIH F31** · RICE UNIVERSITY · 2020 · $15,173

## Abstract

Project summary/Abstract
 Using suppressor analysis to elucidate peroxisome biogenesis and peroxin function
 The import of matrix enzymes that catalyze metabolic reactions supporting growth and development is
central to peroxisome biogenesis and function. The current model for peroxisomal matrix protein import
provides a framework of peroxisomal proteins (peroxins) involved and the associations these peroxins make
to import proteins into the peroxisome. However, this model lacks mechanistic details of the associations
among these peroxins, contributions of non-transport peroxins to import, and possibly unidentified peroxins.
This project proposes using mutant suppression screens to identify new peroxisomal components, reveal
novel genetic interactions between known peroxins, and provide more detailed understanding of known
associations. Mutations in distinct steps in matrix protein import were chosen for suppression screens:
pex12-1, a mutant of a peroxin of the ubiquitin ligating complex that aids in peroxisomal receptor recycling,
and pex14-1 and pex14-6, mutants of a docking complex peroxin that recruits peroxisomal receptors and
aids in matrix protein insertion. In each screen, the initial mutant (pex12-1, pex14-1, or pex14-6) was
mutagenized and then screened for lines with beneficial secondary mutations that alleviated one or more
peroxisomal defects. Numerous mutant suppressors already have been isolated through these screens. For
each prioritized suppressor, this project aims to identify the mutation causing suppression through whole-
genome sequencing, bioinformatics, and recombination mapping. Suppression mechanisms will be
elucidated by combining different mutations and comparing impacts on peroxisome function by monitoring
physiological, cell biological, and molecular responses.
 Characterizing the novel mutations identified in these screens and determining the mechanisms through
which they restore or bypass peroxisome dysfunction will elucidate the roles of the suppressor gene and the
targeted peroxin in peroxisome function and refine our understanding of matrix protein import. Furthermore,
because this project is designed to uncover means of repairing or circumventing peroxisomal dysfunction in
mutants of PEX12 and PEX14 and because peroxins often have conserved function among diverse species,
the results of this proposal may inform therapies for peroxisome biogenesis disorder patients with mutations
that impair docking (PEX14) or ubiquitination (PEX12) of receptor peroxins.
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## Key facts

- **NIH application ID:** 10222444
- **Project number:** 3F31GM125367-03S1
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Roxanna Llinas
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,173
- **Award type:** 3
- **Project period:** 2017-09-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10222444

## Citation

> US National Institutes of Health, RePORTER application 10222444, Using suppressor analysis to elucidate peroxisome biogenesis and peroxin function (3F31GM125367-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10222444. Licensed CC0.

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