Functional mitochondria are required for alpha-synuclein toxicity in aging yeast
Büttner, Sabrina Bitto, Alessandro Ring, Julia Augsten, Manuela Zabrocki, Piotr Eisenberg, Tobias Jungwirth, Helmut Hutter, Sylvia Carmona-Gutierrez, Didac Kroemer, Guido Winderickx, Joris × Madeo, Frank #
Journal of Biological Chemistry vol:283 issue:12 pages:7554-7560
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.