title: Vps35 mediates vesicle transport between the mitochondria and peroxisomes.
abstract: Mitochondria-derived vesicles (MDVs) have been shown to transport cargo from the mitochondria to the peroxisomes. Mitochondria and peroxisomes share common functions in the oxidation of fatty acids and the reduction of damaging peroxides. Their biogenesis is also linked through both the activation of master transcription factors such as PGC-1alpha and the common use of fission machinery, including DRP1, Mff, and hFis1. We have previously shown that MDVs are formed independently of the known mitochondrial fission GTPase Drp1 and are enriched for a mitochondrial small ubiquitin-like modifier (SUMO) E3 ligase called MAPL (mitochondrial-anchored protein ligase). Here, we demonstrate that the retromer complex, a known component of vesicle transport from the endosome to the Golgi apparatus, regulates the transport of MAPL from mitochondria to peroxisomes. An unbiased screen shows that Vps35 and Vps26 are found in complex with MAPL, and confocal imaging reveals Vps35 recruitment to mitochondrial vesicles. Silencing of Vps35 or Vps26A leads to a significant reduction in the delivery of MAPL to peroxisomes, placing the retromer within a novel intracellular trafficking route and providing insight into the formation of MAPL-positive MDVs.
authors.affiliation: University of Ottawa Heart Institute, 40 Ruskin Street, Ottawa, ON K1Y 4W7, Canada.
authors.forename: Emélie
authors.initials: E
authors.lastname: Braschi
authors.forename: Vanessa
authors.initials: V
authors.lastname: Goyon
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Zunino
authors.forename: Abhishek
authors.initials: A
authors.lastname: Mohanty
authors.forename: Liqun
authors.initials: L
authors.lastname: Xu
authors.forename: Heidi M
authors.initials: HM
authors.lastname: McBride
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D002846:Chromatography, Affinity; D002853:Chromatography, Liquid; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D014157:Transcription Factors / Q000378:metabolism; D022161:Transport Vesicles / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; C529067:MUL1 protein, human; D044767:Ubiquitin-Protein Ligases