生物
内质网
细胞器
细胞生物学
液泡
生物发生
酿酒酵母
线粒体
酵母
生物化学
细胞质
基因
作者
Mara Del Vecchio,Lucia Amado,Alexandra P Cogan,Els Meert,Joelle Rosseels,Vanessa Franssens,Sander K. Govers,Joris Winderickx,Ayelén González Montoro
标识
DOI:10.1091/mbc.e23-01-0029
摘要
The protein α-synuclein (α-syn) is one of the major factors linked to Parkinson's disease, yet how its misfolding and deposition contribute to the pathology remains largely elusive. Recently, contact sites among organelles were implicated in the development of this disease. Here, we used the budding yeast Saccharomyces cerevisiae, in which organelle contact sites have been characterized extensively, as a model to investigate their role in α-syn cytotoxicity. We observed that lack of specific tethers that anchor the endoplasmic reticulum to the plasma membrane resulted in cells with increased resistance to α-syn expression. Additionally, we found that strains lacking two dual-function proteins involved in contact sites, Mdm10 and Vps39, were resistant to the expression of α-syn. In the case of Mdm10, we found that this is related to its function in mitochondrial protein biogenesis and not to its role as a contact site tether. In contrast, both functions of Vps39, in vesicular transport and as a tether of the vacuole-mitochondria contact site, were required to support α-syn toxicity. Overall, our findings support that interorganelle communication through membrane contact sites is highly relevant for α-syn-mediated toxicity.
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