國家衛生研究院 NHRI:Item 3990099045/11245
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    題名: Mitochondrial Lon sequesters and stabilizes p53 in the matrix to restrain apoptosis under oxidative stress via its chaperone activity
    作者: Sung, YJ;Kao, TY;Kuo, CL;Fan, CC;Cheng, AN;Fang, WC;Chou, HY;Lo, YK;Chen, CH;Jiang, SS;Chang, IS;Hsu, CH;Lee, JC;Lee, AY
    貢獻者: National Institute of Cancer Research
    摘要: Mitochondrial Lon is a multi-function matrix protease with chaperone activity. However, little literature has been undertaken into detailed investigations on how Lon regulates apoptosis through its chaperone activity. Accumulating evidences indicate that various stresses induce transportation of p53 to mitochondria and activate apoptosis in a transcription-independent manner. Here we found that increased Lon interacts with p53 in mitochondrial matrix and restrains the apoptosis induced by p53 under oxidative stress by rescuing the loss of mitochondrial membrane potential (Deltapsim) and the release of cytochrome C and SMAC/Diablo. Increased chaperone Lon hampers the transcription-dependent apoptotic function of p53 by reducing the mRNA expression of p53 target genes. The ATPase mutant (K529R) of chaperone Lon decreases the interaction with p53 and fails to inhibit apoptosis. Furthermore, the chaperone activity of Lon is important for mitochondrial p53 accumulation in an mtHsp70-dependent manner, which is also important to prevent the cytosolic distribution of p53 from proteasome-dependent degradation. These results indicate that the chaperone activity of Lon is important to bind with mitochondrial p53 by which increased Lon suppresses the apoptotic function of p53 under oxidative stress. Furthermore, mitochondrial Lon-mtHsp70 increases the stability/level of p53 through trafficking and retaining p53 in mitochondrial matrix and preventing the pool of cytosolic p53 from proteasome-dependent degradation in vitro and in clinic.
    日期: 2018-06-13
    關聯: Cell Death and Disease. 2018 Jun 13;9:Article number 697.
    Link to: http://dx.doi.org/10.1038/s41419-018-0730-7
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-4889&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000436579400002
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85048544513
    顯示於類別:[李岳倫] 期刊論文
    [江士昇] 期刊論文
    [張憶壽] 期刊論文

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