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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • PTEN-induced putative kinase

Grant support