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

被引：435

作者：

Matheoud, Diana ^{[1
]}

Sugiura, Ayumu ^{[2
]}

Bellemare-Pelletier, Angelique ^{[1
]}

Laplante, Annie ^{[1
]}

Rondeau, Christiane ^{[1
]}

Chemali, Magali ^{[1
]}

Fazel, Ali ^{[3
]}

Bergeron, John J. ^{[3
]}

Trudeau, Louis-Eric ^{[4
,5
]}

Burelle, Yan ^{[6
]}

Gagnon, Etienne ^{[7
,8
]}

McBride, Heidi M. ^{[2
]}

Desjardins, Michel ^{[1
]}

机构：

[1] Univ Montreal, Dept Pathol & Biol Cellulaire, CP 6128,Succursale Ctr Ville, Montreal, PQ H3C 3J7, Canada

[2] McGill Univ, Montreal Neurol Inst, 3801 Univ St, Montreal, PQ H3A 2B4, Canada

[3] McGill Univ, Dept Med, Hosp Res Inst, Montreal, PQ H4A 3J1, Canada

[4] Univ Montreal, Dept Pharmacol, Montreal, PQ H3C 3J7, Canada

[5] Univ Montreal, Dept Neurosci, Montreal, PQ H3C 3J7, Canada

[6] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada

[7] Univ Montreal, Inst Res Immunol & Canc, Montreal, PQ H3C 3J7, Canada

[8] Univ Montreal, Dept Immunol, Montreal, PQ H3C 3J7, Canada

来源：

CELL | 2016年 / 166卷 / 02期

基金：

日本学术振兴会;

关键词：

PRIMARY BILIARY-CIRRHOSIS; REGULATORY T-CELLS; CLASS-I MOLECULES; MAMMALIAN-CELLS; HEAT-SHOCK; AUTOPHAGY; MITOPHAGY; TRANSPORT; CARGO; RAB9;

D O I：

10.1016/j.cell.2016.05.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：314 / 327

页数：14

共 54 条

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[Anonymous], 2015, EUR POLYM J

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