title: Cargo-selected transport from the mitochondria to peroxisomes is mediated by vesicular carriers.
abstract: Mitochondria and peroxisomes share a number of common biochemical processes, including the beta oxidation of fatty acids and the scavenging of peroxides. Here, we identify a new outer-membrane mitochondria-anchored protein ligase (MAPL) containing a really interesting new gene (RING)-finger domain. Overexpression of MAPL leads to mitochondrial fragmentation, indicating a regulatory function controlling mitochondrial morphology. In addition, confocal- and electron-microscopy studies of MAPL-YFP led to the observation that MAPL is also incorporated within unique, DRP1-independent, 70-100 nm diameter mitochondria-derived vesicles (MDVs). Importantly, vesicles containing MAPL exclude another outer-membrane marker, TOM20, and vesicles containing TOM20 exclude MAPL, indicating that MDVs selectively incorporate their cargo. We further demonstrate that MAPL-containing vesicles fuse with a subset of peroxisomes, marking the first evidence for a direct relationship between these two functionally related organelles. In contrast, a distinct vesicle population labeled with TOM20 does not fuse with peroxisomes, indicating that the incorporation of specific cargo is a primary determinant of MDV fate. These data are the first to identify MAPL, describe and characterize MDVs, and define a new intracellular transport route between mitochondria and peroxisomes.
authors.affiliation: Lipoproteins and Atherosclerosis Group, University of Ottawa Heart Institute, 40 Ruskin St., Ottawa, Ontario K1Y 4W7, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Neuspiel
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Schauss
authors.forename: Emelie
authors.initials: E
authors.lastname: Braschi
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Zunino
authors.forename: Peter
authors.initials: P
authors.lastname: Rippstein
authors.forename: Richard A
authors.initials: RA
authors.lastname: Rachubinski
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Andrade-Navarro
authors.forename: Heidi M
authors.initials: HM
authors.lastname: McBride
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D054829:RING Finger Domains / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
chemical_list: D024101:Mitochondrial Proteins; D014157:Transcription Factors; C529067:MUL1 protein, human; D044767:Ubiquitin-Protein Ligases