Functional mitochondria are required for α-synuclein toxicity in aging yeast

被引：112

作者：

Buettner, Sabrina ^{[1
]}

Bitto, Alessandro ^{[2
]}

Ring, Julia ^{[1
]}

Augsten, Manuela ^{[1
]}

Zabrocki, Piotr ^{[2
]}

Eisenberg, Tobias ^{[1
]}

Jungwirth, Helmut ^{[1
]}

Hutter, Sylvia ^{[1
]}

Carmona-Gutierrez, Didac ^{[1
]}

Kroemer, Guido ^{[3
,4
]}

Winderickx, Joris ^{[2
]}

Madeo, Frank ^{[1
]}

机构：

[1] Graz Univ, Inst Mol Biosci, A-8010 Graz, Austria

[2] Catholic Univ Louvain, B-3000 Louvain, Belgium

[3] Inst Gustave Roussy, INSERM, U848, F-94805 Villejuif, France

[4] Univ Paris 11, F-94805 Villejuif, France

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 12期

关键词：

D O I：

10.1074/jbc.M708477200

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：

alpha-Synuclein is one of the principal toxic triggers of Parkinson disease, an age-associated neurodegeneration. Using old yeast as a model of alpha-synuclein expression in post-mitotic cells, we show that alpha-synuclein toxicity depends on chronological aging and results in apoptosis as well as necrosis. Neither disruption of key components of the unfolded protein response nor deletion of proapoptotic key players (including the yeast caspase YCA1, the apoptosis-inducing factor AIF1, or the serine protease OMI) did prevent alpha-synuclein-induced cell killing. However, abrogation of mitochondrial DNA (rho(0)) inhibited alpha-synuclein-induced reactive oxygen species formation and subsequent apoptotic cell death. Thus, introducing an aging yeast model of alpha-synuclein toxicity, we demonstrate a strict requirement of functional mitochondria.

引用

收藏

页码：7554 / 7560

页数：7

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