Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.
Identifieur interne : 000253 ( Main/Exploration ); précédent : 000252; suivant : 000254Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.
Auteurs : Diana Matheoud [Canada] ; Ayumu Sugiura [Canada] ; Angélique Bellemare-Pelletier [Canada] ; Annie Laplante [Canada] ; Christiane Rondeau [Canada] ; Magali Chemali [Canada] ; Ali Fazel [Canada] ; John J. Bergeron [Canada] ; Louis-Eric Trudeau [Canada] ; Yan Burelle [Canada] ; Etienne Gagnon [Canada] ; Heidi M. Mcbride [Canada] ; Michel Desjardins [Canada]Source :
- Cell [ 1097-4172 ] ; 2016.
English descriptors
- KwdEn :
- Animals, Antigen Presentation, Dendritic Cells (pathology), Disease Models, Animal, Inflammation (metabolism), Macrophages (pathology), Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mitochondria (immunology), Parkinson Disease (immunology), Parkinson Disease (pathology), Protein Kinases (genetics), Protein Kinases (metabolism), Transport Vesicles (metabolism), Ubiquitin-Protein Ligases (genetics), Ubiquitin-Protein Ligases (metabolism).
- MESH :
- chemical , genetics : Protein Kinases, Ubiquitin-Protein Ligases.
- immunology : Mitochondria, Parkinson Disease.
- metabolism : Inflammation, Protein Kinases, Transport Vesicles, Ubiquitin-Protein Ligases.
- pathology : Dendritic Cells, Macrophages, Parkinson Disease.
- Animals, Antigen Presentation, Disease Models, Animal, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL.
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.
DOI: 10.1016/j.cell.2016.05.039
PubMed: 27345367
Affiliations:
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Bergeron</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1</wicri:regionArea><wicri:noRegion>QC H4A 3J1</wicri:noRegion></affiliation></author><author><name sortKey="Trudeau, Louis Eric" sort="Trudeau, Louis Eric" uniqKey="Trudeau L" first="Louis-Eric" last="Trudeau">Louis-Eric Trudeau</name><affiliation wicri:level="1"><nlm:affiliation>Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Burelle, Yan" sort="Burelle, Yan" uniqKey="Burelle Y" first="Yan" last="Burelle">Yan Burelle</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Gagnon, Etienne" sort="Gagnon, Etienne" uniqKey="Gagnon E" first="Etienne" last="Gagnon">Etienne Gagnon</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Mcbride, Heidi M" sort="Mcbride, Heidi M" uniqKey="Mcbride H" first="Heidi M" last="Mcbride">Heidi M. Mcbride</name><affiliation wicri:level="4"><nlm:affiliation>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada. Electronic address: heidi.mcbride@mcgill.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Desjardins, Michel" sort="Desjardins, Michel" uniqKey="Desjardins M" first="Michel" last="Desjardins">Michel Desjardins</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada. 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Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Sugiura, Ayumu" sort="Sugiura, Ayumu" uniqKey="Sugiura A" first="Ayumu" last="Sugiura">Ayumu Sugiura</name><affiliation wicri:level="4"><nlm:affiliation>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Bellemare Pelletier, Angelique" sort="Bellemare Pelletier, Angelique" uniqKey="Bellemare Pelletier A" first="Angélique" last="Bellemare-Pelletier">Angélique Bellemare-Pelletier</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Laplante, Annie" sort="Laplante, Annie" uniqKey="Laplante A" first="Annie" last="Laplante">Annie Laplante</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Rondeau, Christiane" sort="Rondeau, Christiane" uniqKey="Rondeau C" first="Christiane" last="Rondeau">Christiane Rondeau</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Chemali, Magali" sort="Chemali, Magali" uniqKey="Chemali M" first="Magali" last="Chemali">Magali Chemali</name><affiliation wicri:level="1"><nlm:affiliation>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Fazel, Ali" sort="Fazel, Ali" uniqKey="Fazel A" first="Ali" last="Fazel">Ali Fazel</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1</wicri:regionArea><wicri:noRegion>QC H4A 3J1</wicri:noRegion></affiliation></author><author><name sortKey="Bergeron, John J" sort="Bergeron, John J" uniqKey="Bergeron J" first="John J" last="Bergeron">John J. Bergeron</name><affiliation wicri:level="1"><nlm:affiliation>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1</wicri:regionArea><wicri:noRegion>QC H4A 3J1</wicri:noRegion></affiliation></author><author><name sortKey="Trudeau, Louis Eric" sort="Trudeau, Louis Eric" uniqKey="Trudeau L" first="Louis-Eric" last="Trudeau">Louis-Eric Trudeau</name><affiliation wicri:level="1"><nlm:affiliation>Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Burelle, Yan" sort="Burelle, Yan" uniqKey="Burelle Y" first="Yan" last="Burelle">Yan Burelle</name><affiliation wicri:level="1"><nlm:affiliation>Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Gagnon, Etienne" sort="Gagnon, Etienne" uniqKey="Gagnon E" first="Etienne" last="Gagnon">Etienne Gagnon</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Mcbride, Heidi M" sort="Mcbride, Heidi M" uniqKey="Mcbride H" first="Heidi M" last="Mcbride">Heidi M. Mcbride</name><affiliation wicri:level="4"><nlm:affiliation>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada. Electronic address: heidi.mcbride@mcgill.ca.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Desjardins, Michel" sort="Desjardins, Michel" uniqKey="Desjardins M" first="Michel" last="Desjardins">Michel Desjardins</name><affiliation wicri:level="1"><nlm: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.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7</wicri:regionArea><wicri:noRegion>QC H3C 3J7</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell</title><idno type="eISSN">1097-4172</idno><imprint><date when="2016" type="published">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antigen Presentation</term><term>Dendritic Cells (pathology)</term><term>Disease Models, Animal</term><term>Inflammation (metabolism)</term><term>Macrophages (pathology)</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C57BL</term><term>Mitochondria (immunology)</term><term>Parkinson Disease (immunology)</term><term>Parkinson Disease (pathology)</term><term>Protein Kinases (genetics)</term><term>Protein Kinases (metabolism)</term><term>Transport Vesicles (metabolism)</term><term>Ubiquitin-Protein Ligases (genetics)</term><term>Ubiquitin-Protein Ligases (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein Kinases</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Mitochondria</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Inflammation</term><term>Protein Kinases</term><term>Transport Vesicles</term><term>Ubiquitin-Protein Ligases</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Dendritic Cells</term><term>Macrophages</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Antigen Presentation</term><term>Disease Models, Animal</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Mice, Inbred C57BL</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Québec</li></region><settlement><li>Montréal</li></settlement><orgName><li>Université McGill</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Matheoud, Diana" sort="Matheoud, Diana" uniqKey="Matheoud D" first="Diana" last="Matheoud">Diana Matheoud</name></noRegion><name sortKey="Bellemare Pelletier, Angelique" sort="Bellemare Pelletier, Angelique" uniqKey="Bellemare Pelletier A" first="Angélique" last="Bellemare-Pelletier">Angélique Bellemare-Pelletier</name><name sortKey="Bergeron, John J" sort="Bergeron, John J" uniqKey="Bergeron J" first="John J" last="Bergeron">John J. Bergeron</name><name sortKey="Burelle, Yan" sort="Burelle, Yan" uniqKey="Burelle Y" first="Yan" last="Burelle">Yan Burelle</name><name sortKey="Chemali, Magali" sort="Chemali, Magali" uniqKey="Chemali M" first="Magali" last="Chemali">Magali Chemali</name><name sortKey="Desjardins, Michel" sort="Desjardins, Michel" uniqKey="Desjardins M" first="Michel" last="Desjardins">Michel Desjardins</name><name sortKey="Fazel, Ali" sort="Fazel, Ali" uniqKey="Fazel A" first="Ali" last="Fazel">Ali Fazel</name><name sortKey="Gagnon, Etienne" sort="Gagnon, Etienne" uniqKey="Gagnon E" first="Etienne" last="Gagnon">Etienne Gagnon</name><name sortKey="Laplante, Annie" sort="Laplante, Annie" uniqKey="Laplante A" first="Annie" last="Laplante">Annie Laplante</name><name sortKey="Mcbride, Heidi M" sort="Mcbride, Heidi M" uniqKey="Mcbride H" first="Heidi M" last="Mcbride">Heidi M. Mcbride</name><name sortKey="Rondeau, Christiane" sort="Rondeau, Christiane" uniqKey="Rondeau C" first="Christiane" last="Rondeau">Christiane Rondeau</name><name sortKey="Sugiura, Ayumu" sort="Sugiura, Ayumu" uniqKey="Sugiura A" first="Ayumu" last="Sugiura">Ayumu Sugiura</name><name sortKey="Trudeau, Louis Eric" sort="Trudeau, Louis Eric" uniqKey="Trudeau L" first="Louis-Eric" last="Trudeau">Louis-Eric Trudeau</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i -Sk "pubmed:27345367" \
| HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd \
| NlmPubMed2Wicri -a ParkinsonCanadaV1
| This area was generated with Dilib version V0.6.29. |  |