The PEX1 ATPase Stabilizes PEX6 and Plays Essential Roles in Peroxisome Biology

Abstract

A variety of metabolic pathways are sequestered in peroxisomes, conserved organelles that are essential for human and plant survival. Peroxin (PEX) proteins generate and maintain peroxisomes. The PEX1 ATPase facilitates recycling of the peroxisome matrix protein receptor PEX5 and is the most commonly affected peroxin in human peroxisome biogenesis disorders. Here, we describe the isolation and characterization of, to our knowledge, the first Arabidopsis (Arabidopsis thaliana) pex1 missense alleles: pex1-2 and pex1-3. pex1-2 displayed peroxisome-related defects accompanied by reduced PEX1 and PEX6 levels. These pex1-2 defects were exacerbated by growth at high temperature and ameliorated by growth at low temperature or by PEX6 overexpression, suggesting that PEX1 enhances PEX6 stability and vice versa. pex1-3 conferred embryo lethality when homozygous, confirming that PEX1, like several other Arabidopsis peroxins, is essential for embryogenesis. pex1-3 displayed symptoms of peroxisome dysfunction when heterozygous; this semidominance is consistent with PEX1 forming a heterooligomer with PEX6 that is poisoned by pex1-3 subunits. Blocking autophagy partially rescued PEX1/pex1-3 defects, including the restoration of normal peroxisome size, suggesting that increasing peroxisome abundance can compensate for the deficiencies caused by pex1-3 and that the enlarged peroxisomes visible in PEX1/pex1-3 may represent autophagy intermediates. Overexpressing PEX1 in wild-type plants impaired growth, suggesting that excessive PEX1 can be detrimental. Our genetic, molecular, and physiological data support the heterohexamer model of PEX1-PEX6 function in plants.

Disparate peroxisome‐related defects in Arabidopsis pex6 and pex26 mutants link peroxisomal retrotranslocation and oil body utilization

“…PEX1, PEX6, and PEX26 extract PEX5 from the peroxisomal membrane to allow additional rounds of importation (Figure a). Several viable Arabidopsis pex1 (Rinaldi et al ., ), pex6 (Zolman and Bartel, ; Burkhart et al ., ), and pex26 (Goto et al ., ) mutants have been characterized, and comparing these alleles with the pex6‐3, pex6‐4, and pex26‐1 alleles reported here reveals disparate phenotypes that expand our understanding of the functions of PEX6 and PEX26 in plants.…”

Peroxisome Function, Biogenesis, and Dynamics in Plants

“…Interestingly, lon2 and PEX1/pex1-3 peroxisomes appear enlarged, and preventing autophagy restores peroxisome size in both mutants (Farmer et al, 2013;Goto-Yamada et al, 2014;Rinaldi et al, 2017), suggesting that these enlarged peroxisomes are pexophagy intermediates. PEX1 dysfunction in yeast (Nuttall et al, 2014) and mammalian cells (Law et al, 2017) also triggers pexophagy.…”

“…Overexpressing PEX5 worsens the peroxisomal defects of pex1-2 (Rinaldi et al, 2017), pex4-1 (Kao and Bartel, 2015), pex6-2 ), pex6-4 (Gonzalez et al, 2017, and pex26-1 , suggesting that PEX5 impedes peroxisome function when not efficiently recycled. In contrast, overexpressing PEX5 ameliorates pex6-1 (Zolman and Bartel, 2004) and pex6-3 defects.…”

“…pex1-2 displays impaired matrix protein import and low levels of both PEX1 and PEX6 (Rinaldi et al, 2017), suggesting that PEX1 normally stabilizes PEX6. Overexpressing PEX6 restores PEX1 levels and ameliorates pex1-2 peroxisomal defects (Rinaldi et al, 2017), suggesting reciprocal stabilization of PEX1 by PEX6.…”

“…Although PEX1 is the most commonly mutated gene in peroxisome biogenesis disorder patients (for review, see Braverman et al, 2016), Arabidopsis pex1 mutants were only recently reported (Rinaldi et al, 2017). pex1-3 is inviable when homozygous and displays impaired matrix protein import and enlarged peroxisomes when heterozygous (Rinaldi et al, 2017).…”