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Cell. 2016 Jul 14;166(2):314-327. doi: 10.1016/j.cell.2016.05.039. Epub 2016 Jun 23.

Parkinson's Disease-Related Proteins PINK1 and Parkin Repress Mitochondrial Antigen Presentation.

Author information

1
Département de Pathologie et Biologie Cellulaire, Université de Montréal, C.P. 6128, Succursale centre-ville, Montréal, QC H3C 3J7, Canada.
2
Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada.
3
Department of Medicine, McGill University Hospital Research Institute, Montreal, QC H4A 3J1, Canada.
4
Departments of Pharmacology and Neurosciences, Université de Montréal, Montreal, QC H3C 3J7, Canada.
5
Faculty of Pharmacy, Université de Montréal, Montréal, QC H3C 3J7, Canada.
6
Institute for Research in Immunology and Cancer and Department of Immunology, Université de Montréal, Montréal, QC H3C 3J7, Canada.
7
Montreal Neurological Institute, McGill University, 3801 University Avenue, Montreal, QC H3A 2B4, Canada. Electronic address: heidi.mcbride@mcgill.ca.
8
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.

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.

PMID:
27345367
DOI:
10.1016/j.cell.2016.05.039
[Indexed for MEDLINE]
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