De novo formation and maintenance of mammalian peroxisomes in cultured PEX16-knockout cells generated by CRISPR/Cas9

Mammalian PEX16 has been considered essential for generating and maintaining peroxisomal membranes. This view is based primarily on the finding that fibroblasts from several PEX16-deficient patients are devoid of peroxisomal structures but can form peroxisomes upon expression of PEX16. However, unlike these patient-derived cells, pex16 mutants in other model organisms contain partially functional peroxisomes. Here, we report that PEX16-knockout (KO) cells derived from three mammalian cultured cell lines comprise cells containing a fewer number of enlarged peroxisomes and cells lacking peroxisomes. We also suggest that PEX16 accelerates the process by which peroxisome-less cells form peroxisomal membranes and subsequently establish mature peroxisomes, independently of its ability to mediate peroxisomal targeting of PEX3. Nevertheless, PEX16 is not absolutely required for this process. Moreover, a wellknown patient-derived PEX16 mutant inhibits the de novo formation of peroxisomal membranes. Our findings suggest that although PEX16 is undoubtedly important for optimal peroxisomal membrane biogenesis, mammalian cells may be able to form peroxisomes de novo and maintain the organelles without the aid of PEX16.

Automated summary

Previously, mammalian PEX16 was believed to be essential for peroxisomal membrane biogenesis and maintenance. However, recent studies found that pex16 mutants in other model organisms still have partially functional peroxisomes. It was also discovered that PEX16 accelerates the process of forming peroxisomal membranes in peroxisome-less cells, independently of its role in mediating peroxisomal targeting of PEX3.