线粒体
细胞生物学
内质网
黑腹果蝇
爪蟾
生物
未折叠蛋白反应
帕金森病
化学
作者
Marie Paradis,Nicole Kucharowski,Gabriela Edwards,Santiago Maya Palacios,Christian Meyer,Birgit Stümpges,Isabell Jamitzky,Julia Kalinowski,Christoph Thiele,Reinhard Bauer,Achim Paululat,Julia Sellin,Margret H. Bülow
标识
DOI:10.21203/rs.3.rs-911428/v1
摘要
Abstract Dynamic contacts are formed between endoplasmic reticulum (ER) and mitochondria that enable the exchange of calcium and phospholipids. Disturbed contacts between ER and mitochondria impair mitochondrial dynamics and are a molecular hallmark of Parkinson’s disease. Cystein-rich with EGF-like domain (Creld) are ER-proteins associated with atrioventricular septal defects, but human CRELD1 is also a poorly characterized risk gene for Parkinson’s disease. Here we show that Creld is required for ER-mitochondria communication. Loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in Drosophila melanogaster, Xenopus tropicalis and human cells. We found that reduced respiratory complex I activity lowers hydrogen peroxide levels, which disturbs neuronal activity and leads to impaired locomotion in Creld mutants. Our study presents a new paradigm of neuron dysfunction as a result of impaired ER-mitochondria communication and a new model for Parkinson’s disease.
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