线粒体
细胞生物学
神经退行性变
黑腹果蝇
内质网
生物
爪蟾
化学
作者
Marie Paradis,Nicole Kucharowski,Gabriela Edwards-Faret,Santiago José Maya Palacios,Christian Meyer,Birgit Stümpges,Isabell Jamitzky,Julia Kalinowski,Christoph Thiele,Reinhard Bauer,Achim Paululat,Julia Sellin,Margret H. Bülow
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2022-07-22
卷期号:8 (29)
标识
DOI:10.1126/sciadv.abo0155
摘要
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, which is also characterized by impaired complex I activity and dopaminergic neuron degeneration. Here, we analyzed the role of cysteine-rich with EGF-like domain (Creld), a poorly characterized risk gene for Parkinson’s disease, in the regulation of mitochondrial dynamics and function. We found that loss of Creld leads to mitochondrial hyperfusion and reduced ROS signaling in Drosophila melanogaster , Xenopus tropicalis , and human cells. Creld fly mutants show differences in ER-mitochondria contacts and reduced respiratory complex I activity. The resulting low–hydrogen peroxide levels are linked to disturbed neuronal activity and lead to impaired locomotion, but not neurodegeneration, in Creld mutants. We conclude that Creld regulates ER-mitochondria communication and thereby hydrogen peroxide formation, which is required for normal neuron function.
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