Pex24 and Pex32 tether peroxisomes to the ER for organelle biogenesis, positioning and segregation

We analyzed all four Pex23 family proteins of the yeast Hansenula polymorpha, which localize to the ER. Of these Pex24 and Pex32, but not Pex23 and Pex29, accumulate at peroxisome-ER contacts, where they are important for normal peroxisome biogenesis and proliferation and contribute to organelle positioning and segregation. Upon deletion of PEX24 and PEX32 - and to a lesser extent of PEX23 and PEX29 - peroxisome-ER contacts are disrupted, concomitant with peroxisomal defects. These defects are suppressed upon introduction of an artificial peroxisome-ER tether. Accumulation of Pex32 at peroxisomes-ER contacts is lost in the absence of the peroxisomal membrane protein Pex11. At the same time peroxisome-ER contacts are disrupted, indicating that Pex11 contributes to Pex32-dependent peroxisome-ER contact formation. Summarizing, our data indicate that H. polymorpha Pex24 and Pex32 are tethers at peroxisome-ER contacts that are important for normal peroxisome biogenesis and dynamics. SummaryTwo Hansenula polymorpha ER proteins, Pex24 and Pex32, are tethers at peroxisome-ER contacts and function together with the peroxisomal protein Pex11. Their absence disturbs these contacts leading to multiple peroxisomal defects, which can be restored by an artificial tether.