Zinc cooperates with p53 to inhibit the activity of mitochondrial aconitase through reactive oxygen species accumulation
Zinc cooperates with p53 to inhibit the activity of mitochondrial aconitase through reactive oxygen species accumulation
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锌与p53配合通过活性氧积累抑制线粒体乌头酸酶的活性
DOI：
10.1002/cam4.2130
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发表时间：
2019-05-01
期刊：
影响因子：
4
通讯作者：
Li, Yang
中科院分区：
文献类型：
--
作者：
Xue, Ya-Nan;Liu, Ya-Nan;Li, Yang
代谢重编程是癌症的一个主要标志。因此，靶向代谢可能提供一种有效的策略，用于确定有前途的药物靶点用于癌症治疗。在前列腺癌中，细胞经历从锌积累、柠檬酸盐产生细胞到具有较低锌水平和较高线粒体顺乌头酸酶（ACO2）活性的柠檬酸盐氧化恶性细胞的代谢转化。ACO2是一种将柠檬酸盐转化为异柠檬酸盐的克雷布斯循环酶，对活性氧（ROS）介导的损伤敏感。在本研究中，我们发现ACO2的表达与前列腺癌的恶性程度呈正相关。锌和p53都可以导致ROS的增加。ACO2可以通过感知前列腺癌ROS水平的变化而成为重塑代谢的靶点。我们的研究结果表明，通过锌和p53靶向ACO2可以改变前列腺癌的代谢，从而为前列腺癌提供了一种潜在的新的治疗策略。
Metabolic reprogramming is a central hallmark of cancer. Therefore, targeting metabolism may provide an effective strategy for identifying promising drug targets for cancer treatment. In prostate cancer, cells undergo metabolic transformation from zinc-accumulating, citrate-producing cells to citrate-oxidizing malignant cells with lower zinc levels and higher mitochondrial aconitase (ACO2) activity. ACO2 is a Krebs cycle enzyme that converts citrate to isocitrate and is sensitive to reactive oxygen species (ROS)-mediated damage. In this study, we found that the expression of ACO2 is positively correlated with the malignancy of prostate cancer. Both zinc and p53 can lead to an increase in ROS. ACO2 can be a target for remodeling metabolism by sensing changes in the ROS levels of prostate cancer. Our results indicate that targeting ACO2 through zinc and p53 can change prostate cancer metabolism, and thus provides a potential new therapeutic strategy for prostate cancer.