A pex1 missense mutation improves peroxisome function in a subset of Arabidopsis pex6 mutants without restoring PEX5 recycling

Significance ATPases have diverse cellular roles, including extracting proteins from membranes to maintain organellar function. The PEX1–PEX6 heterohexameric ATPases are thought to retrotranslocate PEX5 from the peroxisome membrane, and PEX1–PEX6 dysfunction impairs peroxisome biogenesis in humans and plants. We implemented a pex6 suppressor screen in Arabidopsis and recovered a compensatory pex1 allele that rescues several pex6 defects. Preventing autophagy also improved pex6 peroxisome function, and combining the pex1 and autophagy lesions delivered synergistic benefits. Surprisingly, these different alterations ameliorated pex6 symptoms without notably restoring the sole known function of PEX6, suggesting that PEX1–PEX6 has unexplored functions. Because the pex6 mutations ameliorated by pex1 are analogous to those in human pex6 patients, this study informs research on peroxisome dysfunction in other eukaryotes.