Details

Autor(en) / Beteiligte

• Guder, Philipp
• Lotz-Havla, Amelie S.
• Woidy, Mathias
• Reiß, Dunja D.
• Danecka, Marta K.
• Schatz, Ulrich A.
• Becker, Marc
• Ensenauer, Regina
• Pagel, Philipp
• Büttner, Lars
• Muntau, Ania C.
• Gersting, Søren W.

Titel

Isoform-specific domain organization determines conformation and function of the peroxisomal biogenesis factor PEX26

Ist Teil von

• Biochimica et biophysica acta. Molecular cell research, 2019-03, Vol.1866 (3), p.518-531

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2019

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• Peroxisomal biogenesis factor PEX26 is a membrane anchor for the multi-subunit PEX1-PEX6 protein complex that controls ubiquitination and dislocation of PEX5 cargo receptors for peroxisomal matrix protein import. PEX26 associates with the peroxisomal translocation pore via PEX14 and a splice variant (PEX26Δex5) of unknown function has been reported. Here, we demonstrate PEX26 homooligomerization mediated by two heptad repeat domains adjacent to the transmembrane domain. We show that isoform-specific domain organization determines PEX26 oligomerization and impacts peroxisomal β-oxidation and proliferation. PEX26 and PEX26Δex5 displayed different patterns of interaction with PEX2-PEX10 or PEX13-PEX14 complexes, which relate to distinct pre-peroxisomes in the de novo synthesis pathway. Our data support an alternative PEX14-dependent mechanism of peroxisomal membrane association for the splice variant, which lacks a transmembrane domain. Structure-function relationships of PEX26 isoforms explain an extended function in peroxisomal homeostasis and these findings may improve our understanding of the broad phenotype of PEX26-associated human disorders. •C-tail membrane anchored PEX26 recruits PEX1-PEX6 complexes to peroxisomes.•Peroxisomal PEX26 homooligomerization is mediated by two heptad repeat domains.•Isoform-specific domain organization determines PEX26 oligomerization and impacts peroxisomal β-oxidation and proliferation.•A splice variant, lacking a transmembrane domain, associates with peroxisomes by an alternative PEX14-dependent mechanism.