Peroxisomes are cellular organelles with vital functions in lipid, amino acid and redox metabolism. The cellular formation and dynamics of peroxisomes are governed by PEX genes; however, the regulation of peroxisome abundance is still poorly understood. Here, we use a high-content microscopy screen in Saccharomyces cerevisiae to identify new regulators of peroxisome size and abundance. Our screen led to the identification of a previously uncharacterized gene, which we term PEX35, which affects peroxisome abundance. PEX35 encodes a peroxisomal membrane protein, a remote homolog to several curvature-generating human proteins. We systematically characterized the genetic and physical interactome as well as the metabolome of mutants in PEX35, and we found that Pex35 functionally interacts with the vesicle-budding-inducer Arf1. Our results highlight the functional interaction between peroxisomes and the secretory pathway.
The authors declare no competing or financial interests.
M.S. and S.T. conceived the study. I.Y., T.P.D., C.S.E., M.S., E.Z. and S.T. conceived and supervised the experiments. I.Y. performed the majority of the experiments in this manuscript. S. Chuartzman performed the high content screen. K.S. performed the STED experiments and the oleate growth assays. B.M. and T.P.D. measured the redox status of peroxisomes. C.J.E. performed the lipidomics analysis. S.T. performed peroxisome purification. S. Cooper, K.S. and S.T. conducted amino acid analyses. All authors analyzed the data. I.Y., M.S., E.Z. and S.T. wrote the manuscript.
This work was supported by the State of Lower-Saxony, Hannover, Germany [ZN2921 to M.S. and S.T.], and by the European Research Council [CoG 646604 to M.S.]. Maya Schuldiner is an incumbent of the Dr Gilbert Omenn and Martha Darling Professorial Chair in Molecular Genetics.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.187914.supplemental
- Received February 10, 2016.
- Accepted November 24, 2016.
- © 2017. Published by The Company of Biologists Ltd