Parkinson’s Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation
| Autor: | Christiane Rondeau, Heidi M. McBride, Yan Burelle, Diana Matheoud, Ayumu Sugiura, Michel Desjardins, Angelique Bellemare-Pelletier, Annie Laplante, John J.M. Bergeron, Ali Fazel, Magali Chemali, Louis-Eric Trudeau, Etienne Gagnon |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases Antigen presentation PINK1 Mitochondrion Biology General Biochemistry Genetics and Molecular Biology Parkin Immune tolerance Mice 03 medical and health sciences Immune system Mitophagy Animals Transport Vesicles Inflammation Antigen Presentation Mice Inbred BALB C Macrophages Autophagy Parkinson Disease Dendritic Cells Mitochondria nervous system diseases Cell biology Mice Inbred C57BL Disease Models Animal 030104 developmental biology Protein Kinases |
| Zdroj: | Cell. 166:314-327 |
| ISSN: | 0092-8674 |
| DOI: | 10.1016/j.cell.2016.05.039 |
| Popis: | Summary 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. |
| Databáze: | OpenAIRE |
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