Department of Biochemistry and Molecular Biology, School of Medicine, Neurochemistry Research Institute, Complutense University of Madrid, Spain.
CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, Madrid, Spain.
FEBS J. 2024 Jun;291(12):2562-2564. doi: 10.1111/febs.17155. Epub 2024 May 6.
Around 10% of Parkinson's disease (PD) cases are associated with mutations in various genes, including FBXO7, which encodes the substrate-recognition component for the Skp1-Cullin-F-box (SCF) class of ubiquitin E3 ligases that target proteins for proteasomal degradation. In their recent study, Al Rawi et al. characterized a new mutation in FBXO7, L250P, in a pediatric patient. Their findings reveal that the L250P mutation abolishes Fbxo7 interaction with the proteasome regulator, proteasome inhibitor 31kD (PI31), affecting proteasomal activity and the ubiquitination of some of the ligase's targets. Furthermore, the authors show that this previously undescribed mutation impairs mitochondrial function and mitophagy, emphasizing the importance of mitochondrial and proteasomal dysfunction in PD pathogenesis.
约 10%的帕金森病（PD）病例与各种基因突变有关，包括 FBXO7，它编码 Skp1-Cullin-F-box（SCF）类泛素 E3 连接酶的底物识别组件，该酶可将蛋白质靶向蛋白酶体降解。在他们的最新研究中，Al Rawi 等人在一名儿科患者中鉴定出 FBXO7 的一个新突变 L250P。他们的发现表明，L250P 突变会破坏 Fbxo7 与蛋白酶体调节剂、蛋白酶体抑制剂 31kD（PI31）的相互作用，从而影响蛋白酶体的活性和该连接酶的一些靶标的泛素化。此外，作者表明，这种先前未描述的突变会损害线粒体功能和线粒体自噬，强调了线粒体和蛋白酶体功能障碍在 PD 发病机制中的重要性。
