title: PEX11 family members are membrane elongation factors that coordinate peroxisome proliferation and maintenance.
abstract: Dynamic changes of membrane structure are intrinsic to organelle morphogenesis and homeostasis. Ectopic expression of proteins of the PEX11 family from yeast, plant or human lead to the formation of juxtaposed elongated peroxisomes (JEPs),which is evocative of an evolutionary conserved function of these proteins in membrane tubulation. Microscopic examinations reveal that JEPs are composed of independent elongated peroxisomes with heterogeneous distribution of matrix proteins. We established the homo- and heterodimerization properties of the human PEX11 proteins and their interaction with the fission factor hFis1, which is known to recruit the GTPase DRP1 to the peroxisomal membrane. We show that excess of hFis1 but not of DRP1 is sufficient to fragment JEPs into normal round-shaped organelles, and illustrate the requirement of microtubules for JEP formation. Our results demonstrate that PEX11-induced JEPs represent intermediates in the process of peroxisome membrane proliferation and that hFis1 is the limiting factor for progression. Hence, we propose a model for a conserved role of PEX11 proteins in peroxisome maintenance through peroxisome polarization, membrane elongation and segregation.
authors.affiliation: Max F. Perutz Laboratories, Center of Molecular Biology, University of Vienna, Department of Biochemistry and Cell Biology, Dr Bohr-Gasse 9, 1030, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Koch
authors.forename: Kornelija
authors.initials: K
authors.lastname: Pranjic
authors.forename: Anja
authors.initials: A
authors.lastname: Huber
authors.forename: Adolf
authors.initials: A
authors.lastname: Ellinger
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartig
authors.forename: Friedrich
authors.initials: F
authors.lastname: Kragler
authors.forename: Cécile
authors.initials: C
authors.lastname: Brocard
mesh_terms: D022081:Cell Surface Extensions / Q000378:metabolism* / Q000473:pathology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D005818:Genetic Engineering; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D055503:Protein Multimerization; D034741:RNA, Small Interfering / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D014026:Nicotiana
chemical_list: C476525:FIS1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; C490455:PEX11A protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins