title: Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.
abstract: Antigen presentation is essential for establishing immune tolerance and for immune responses against infectious disease and cancer. Although antigen presentation can be mediated by autophagy, here we demonstrate a pathway for mitochondrial antigen presentation (MitAP) that relies on the generation and trafficking of mitochondrial-derived vesicles (MDVs) rather than on autophagy/mitophagy. We find that PINK1 and Parkin, two mitochondrial proteins linked to Parkinson's disease (PD), actively inhibit MDV formation and MitAP. In absence of PINK1 or Parkin, inflammatory conditions trigger MitAP in immune cells, both in vitro and in vivo. MitAP and the formation of MDVs require Rab9 and Sorting nexin 9, whose recruitment to mitochondria is inhibited by Parkin. The identification of PINK1 and Parkin as suppressors of an immune-response-eliciting pathway provoked by inflammation suggests new insights into PD pathology.
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Matheoud
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Sugiura
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Angélique
authors.initials: A
authors.lastname: Bellemare-Pelletier
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Laplante
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Christiane
authors.initials: C
authors.lastname: Rondeau
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
authors.forename: Magali
authors.initials: M
authors.lastname: Chemali
authors.affiliation: Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.
authors.forename: Ali
authors.initials: A
authors.lastname: Fazel
authors.affiliation: Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.
authors.forename: John J
authors.initials: JJ
authors.lastname: Bergeron
authors.affiliation: Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7, Canada.
authors.forename: Louis-Eric
authors.initials: LE
authors.lastname: Trudeau
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Burelle
authors.affiliation: Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
authors.forename: Etienne
authors.initials: E
authors.lastname: Gagnon
authors.affiliation: Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada. Electronic address: heidi.mcbride@mcgill.ca.
authors.forename: Heidi M
authors.initials: HM
authors.lastname: McBride
authors.affiliation: Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada. Electronic address: michel.desjardins@umontreal.ca.
authors.forename: Michel
authors.initials: M
authors.lastname: Desjardins
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000473:pathology; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000276:immunology*; D010300:Parkinson Disease / Q000276:immunology* / Q000473:pathology; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein