國家衛生研究院 NHRI:Item 3990099045/13695
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    題名: UQCRC1 engages cytochrome C for neuronal apoptotic cell death
    作者: Hung, YC;Huang, KL;Chen, PL;Li, JL;Lu, SHA;Chang, JC;Lin, HY;Lo, WC;Huang, SY;Lee, TT;Lin, TY;Imai, Y;Hattori, N;Liu, CS;Tsai, SY;Chen, CH;Lin, CH;Chan, CC
    貢獻者: National Institute of Infectious Diseases and Vaccinology
    摘要: Human ubiquinol-cytochrome c reductase core protein 1 (UQCRC1) is an evolutionarily conserved core subunit of mitochondrial respiratory chain complex III. We recently identified the disease-associated variants of UQCRC1 from patients with familial parkinsonism, but its function remains unclear. Here we investigate the endogenous function of UQCRC1 in the human neuronal cell line and the Drosophila nervous system. Flies with neuronal knockdown of uqcrc1 exhibit age-dependent parkinsonism-resembling defects, including dopaminergic neuron reduction and locomotor decline, and are ameliorated by UQCRC1 expression. Lethality of uqcrc1-KO is also rescued by neuronally expressing UQCRC1, but not the disease-causing variant, providing a platform to discern the pathogenicity of this mutation. Furthermore, UQCRC1 associates with the apoptosis trigger cytochrome c (cyt-c), and uqcrc1 deficiency increases cyt-c in the cytoplasmic fraction and activates the caspase cascade. Depleting cyt-c or expression of the anti-apoptotic p35 ameliorates uqcrc1-mediated neurodegeneration. Our findings identify a role for UQCRC1 in regulating cyt-c-induced apoptosis.
    日期: 2021-09-21
    關聯: Cell Reports. 2021 Sep 21;36(12):Article number 109729.
    Link to: http://dx.doi.org/10.1016/j.celrep.2021.109729
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2211-1247&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000698680800012
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85115414235
    顯示於類別:[陳俊宏] 期刊論文

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