品脱1
粒体自噬
生物
自噬
泛素连接酶
泛素
帕金
细胞生物学
线粒体
基础(医学)
帕金森病
神经科学
疾病
内科学
内分泌学
细胞凋亡
遗传学
医学
基因
胰岛素
作者
Jens O. Watzlawik,Fabienne C. Fiesel,Gabriella Fiorino,Bernardo A. Bustillos,Zahra Baninameh,Briana N. Markham,Xu Hou,Caleb S. Hayes,Jenny M. Bredenberg,Nicholas Kurchaba,Dominika Fričová,Joanna Siuda,Zbigniew K. Wszołek,Shinichi Noda,Shigeto Sato,Nobutaka Hattori,Asheeta A. Prasad,Deniz Kirik,Howard S. Fox,Kelly L. Stauch,Matthew S. Goldberg,Wolfdieter Springer
出处
期刊:Autophagy
[Informa]
日期:2023-12-02
卷期号:: 1-12
标识
DOI:10.1080/15548627.2023.2286414
摘要
The ubiquitin kinase-ligase pair PINK1-PRKN recognizes and transiently labels damaged mitochondria with ubiquitin phosphorylated at Ser65 (p-S65-Ub) to mediate their selective degradation (mitophagy). Complete loss of PINK1 or PRKN function unequivocally leads to early-onset Parkinson disease, but it is debated whether impairments in mitophagy contribute to disease later in life. While the pathway has been extensively studied in cell culture upon acute and massive mitochondrial stress, basal levels of activation under endogenous conditions and especially in vivo in the brain remain undetermined. Using rodent samples, patient-derived cells, and isogenic neurons, we here identified age-dependent, brain region-, and cell type-specific effects and determined expression levels and extent of basal and maximal activation of PINK1 and PRKN. Our work highlights the importance of defining critical risk and therapeutically relevant levels of PINK1-PRKN signaling which will further improve diagnosis and prognosis and will lead to better stratification of patients for future clinical trials.
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