Dataset Information

PEX16 contributions to peroxisome import and metabolism revealed by viable Arabidopsis pex16 mutants.

ABSTRACT: Peroxisomes rely on peroxins (PEX proteins) for biogenesis, importing membrane and matrix proteins, and fission. PEX16, which is implicated in peroxisomal membrane protein targeting and forming nascent peroxisomes from the endoplasmic reticulum (ER), is unusual among peroxins because it is inserted co-translationally into the ER and localizes to both ER and peroxisomal membranes. PEX16 mutations in humans, yeast, and plants confer some common peroxisomal defects; however, apparent functional differences have impeded the development of a unified model for PEX16 action. The only reported pex16 mutant in plants, the Arabidopsis shrunken seed1 mutant, is inviable, complicating analysis of PEX16 function after embryogenesis. Here, we characterized two viable Arabidopsis pex16 alleles that accumulate negligible PEX16 protein levels. Both mutants displayed impaired peroxisome function - slowed consumption of stored oil bodies, decreased import of matrix proteins, and increased peroxisome size. Moreover, one pex16 allele exhibited reduced growth that could be alleviated by an external fixed carbon source, decreased responsiveness to peroxisomally processed hormone precursors, and worsened or improved peroxisome function in combination with other pex mutants. Because the mutations impact different regions of the PEX16 gene, these viable pex16 alleles allow assessment of the importance of Arabidopsis PEX16 and its functional domains.

SUBMITTER: Burkhart SE

PROVIDER: S-EPMC6613983 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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PEX16 contributions to peroxisome import and metabolism revealed by viable Arabidopsis pex16 mutants.

Burkhart Sarah E SE Llinas Roxanna J RJ Bartel Bonnie B

Journal of integrative plant biology 20190403 7

Peroxisomes rely on peroxins (PEX proteins) for biogenesis, importing membrane and matrix proteins, and fission. PEX16, which is implicated in peroxisomal membrane protein targeting and forming nascent peroxisomes from the endoplasmic reticulum (ER), is unusual among peroxins because it is inserted co-translationally into the ER and localizes to both ER and peroxisomal membranes. PEX16 mutations in humans, yeast, and plants confer some common peroxisomal defects; however, apparent functional dif ...[more]

PMID: 30761735

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Project description:Peroxisome biogenesis diseases (PBDs) are characterized by global defects in peroxisomal function and can result in severe brain, liver, kidney, and bone malfunctions. PBDs are due to mutations in peroxisome biogenesis factors (PEX genes) that are responsible for peroxisome assembly and function. Increasing evidence suggests that peroxisome import functions decline during aging. However, the transcriptome profiling of peroxisome import defects and how they affect disease development are still lacking. PEX5 encodes the cytoplasmic receptors for peroxisome-targeting signal types 1. We generate knock-in human HEK293 cells mutant using CRISPR to transiently express PEX5 cysteine 11 to alanine mutant (PEX5C11A), which blocks PEX5 recycling and exerts dominant negative effect on PEX5 mediated peroxisome import. To identify conserved responses, we perform transcriptomic analysis on Drosophila oenocyte-specific Pex1, Pex12 and Pex5 knockdowns and on human cells with impaired peroxisome import (through expressing PEX5C11A and applying PEX5 siRNA respectively). PEX5C11A induction triggers vast transcriptomic changes, including decreased oxidative phosphorylation, increased MAPK signaling and HIPPO signaling. PEX5 siRNA specifically decreases spliceosome activity and increases cholesterol metabolism. Using gene set enrichment analysis (GSEA), we identify protein processing in endoplasmic reticulum pathway, specifically ER-associated protein degradation (ERAD) pathway is induced in all PEX knockdowns in Drosophila. Peroxisome dysfunction elevates eIF2α phosphorylation in both Drosophila and human cell culture independent of XBP1 activation, suggesting increased integrative stress response (ISR). Moreover, peroxisome stress decreases ribosome biogenesis genes and impairs ribosome biogenesis in flies and human cells. Specifically, peroxisome stress impairs the 5'-ETS cleavage activity during the ribosome biogenesis and dampens 40S small ribosomal export in both flies and human. Our results suggest that reduced ribosome biogenesis and elevated ISR could be conserved cellular response to peroxisome import stress.

Dataset Information

PEX16 contributions to peroxisome import and metabolism revealed by viable Arabidopsis pex16 mutants.

Publications

PEX16 contributions to peroxisome import and metabolism revealed by viable Arabidopsis pex16 mutants.

Similar Datasets

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