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Functional mitochondria are required for alpha-synuclein toxicity in aging yeast.
J Biol Chem. 2008 Mar 21; 283(12):7554-60
Heinz Osiewacz, Institute of Molecular Biosciences, Germany. F1000 Microbiology
24 Jul 2008 | New Finding, Technical Advance
This article reports the demonstration of how a biological system like yeast can successfully be used to obtain significant new data about a component that, in humans, plays a role in disease development.
Using yeast, the authors show that alpha-synuclein, which in humans is involved in triggering Parkinsons's disease, requires functional mitochondria.
The used strategy may be followed to investigate also other biological questions utilizing experimentally tractable in-vivo systems.
Competing interests: None declared
Osiewacz H: "This article reports the demonstration of how a biological system like yeast can successfully be..." Evaluation of: [Büttner S et al. Functional mitochondria are required for alpha-synuclein toxicity in aging yeast. J Biol Chem. 2008 Mar 21; 283(12):7554-60; doi: 10.1074/jbc.M708477200]. Faculty of 1000, 24 Jul 2008. F1000.com/1115786#eval571870
Short form
Osiewacz H: 2008. F1000.com/1115786#eval571870
Faculty of 1000 evaluations, dissents and comments for [Büttner S et al. Functional mitochondria are required for alpha-synuclein toxicity in aging yeast. J Biol Chem. 2008 Mar 21; 283(12):7554-60; doi: 10.1074/jbc.M708477200]. Faculty of 1000, 24 Jul 2008. F1000.com/1115786
Short form
Faculty of 1000: 2008. F1000.com/1115786
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.
DOI: 10.1074/jbc.M708477200
PMID: 18192273
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