p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases.
p53 and mitochondrial dysfunction: novel insight of neurodegenerative diseases.
复制标题
p53 和线粒体功能障碍：神经退行性疾病的新见解
DOI：
10.1007/s10863-016-9669-5
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发表时间：
2016-08
影响因子：
3
通讯作者：
Wang, Ya-Yun
中科院分区：
文献类型：
--
作者：
Dai, Chun-Qiu;Luo, Ting-Ting;Luo, Shi-Cheng;Wang, Jia-Qi;Wang, Sheng-Ming;Bai, Yun-Hu;Yang, Yan-Ling;Wang, Ya-Yun
关键词：
线粒体是负责重要细胞功能的细胞器。 p53 是调节 DNA 稳定性和细胞正常生长的转录因子。最近的研究表明，p53可以影响不同应激水平下线粒体功能从正常状态向异常状态的转变。正常状态下，p53可以通过SCO2的反式激活来维持线粒体呼吸。当应激刺激出现时，SCO2 过度表达并导致 ROS 生成。 ROS 促进 p53 诱导的 MALM（Mieap 诱导的线粒体内溶酶体样细胞器的积累）来修复功能失调的线粒体和 MIV（Mieap 诱导的液泡）以完成受损的线粒体降解。如果压力或损伤是不可逆的，p53 将易位到线粒体，导致细胞凋亡或坏死。帕金森病、亨廷顿病和阿尔茨海默病等神经退行性疾病的机制尚缺乏明确的解释，但更多的研究揭示了线粒体和p53在这些疾病病理发展中的功能关系。本文综述了p53在线粒体功能的病理代谢方面发挥的重要作用。我们还用与p53和线粒体相关的新型靶向治疗分子来分析这些疾病，希望在未来的临床中提出新的治疗方法。
Mitochondria are organelles responsible for vital cell functions. p53 is a transcription factor that regulates the DNA stability and cell growth normality. Recent studies revealed that p53 can influence mitochondrial function changing from normal condition to abnormal condition under different stress levels. In normal state, p53 can maintain mitochondrial respiration through transactivation of SCO2. When stress stimuli presents, SCO2 overexpresses and leads to ROS generation. ROS promotes p53 inducing MALM (Mieap-induced accumulation of lysosome-like organelles within mitochondria) to repair dysfunctional mitochondria and MIV (Mieap-induced vacuole) to accomplish damaged mitochondria degradation. If stress or damage is irreversible, p53 will translocate to mitochondria, leading into apoptosis or necrosis. Neurodegenerative diseases including Parkinson’s disease, Huntington’s disease and Alzheimer’s disease are still lack of clear explanations of mechanisms, but more studies have revealed the functional relationship between mitochondria and p53 towards the pathological development of these diseases. In this review, we discuss that p53 plays the vital role in the function of mitochondria in the aspect of pathological change metabolism. We also analyze these diseases with novel targeted treating molecules which are related to p53 and mitochondria, hoping to present novel therapies in future clinic.
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DOI：
10.1155/2015/527209
发表时间：
2015
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Gibellini L;Bianchini E;De Biasi S;Nasi M;Cossarizza A;Pinti M
通讯作者：
Pinti M
DOI：
10.3233/jad-130761
发表时间：
2013
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Manczak M;Sheiko T;Craigen WJ;Reddy PH
通讯作者：
Reddy PH
影响因子：
6.2
作者：
Kamino H;Nakamura Y;Tsuneki M;Sano H;Miyamoto Y;Kitamura N;Futamura M;Kanai Y;Taniguchi H;Shida D;Kanemitsu Y;Moriya Y;Yoshida K;Arakawa H
通讯作者：
Arakawa H
影响因子：
5.2
作者：
Lee SK;Kim YS
通讯作者：
Kim YS
影响因子：
7.4
作者：
Hernlund, Emma;Kutuk, Ozgur;Shoshan, Maria
通讯作者：
Shoshan, Maria