Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.
Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.
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DOI：
10.3390/ijms24065564
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发表时间：
2023-03-14
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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癌症已逐渐成为全球主要的健康问题。随着这种全球关注的发展，癌症威慑是这个时代最重大的公共卫生挑战之一。到目前为止，科学界无疑强调线粒体功能障碍是癌细胞的标志。线粒体膜的通透性已被认为是凋亡介导的癌细胞死亡中最重要的足迹。在线粒体钙超载的条件下，线粒体钙超载完全由氧化应激介导，线粒体膜上开放一条直径明确的非特异性通道，允许线粒体基质与高达1.5 kDa的额外线粒体溶质和蛋白质的胞浆自由交换。这种通道/非特异孔被认为是线粒体通透性转换孔(MPTP)。MPTP已被建立用于调控凋亡介导的癌细胞死亡。已有研究表明，MPTP与糖酵解酶己糖激酶II密切相关，可防御细胞死亡和减少细胞色素c的释放。然而，线粒体Ca~(2+)负荷增加、氧化应激和线粒体去极化是导致MPTP开放/激活的关键因素。尽管MPTP介导的细胞死亡的确切机制仍不清楚，但MPTP介导的细胞凋亡机制已被认为是一种重要的钳制机制，在几种类型的癌症的发病机制中发挥着关键作用。在这篇综述中，我们重点介绍MPTP复合体介导的细胞凋亡机制的结构和调控，并对新型MPTP靶向药物/分子在癌症治疗中的发展进行全面的讨论。
Cancer has been progressively a major global health concern. With this developing global concern, cancer determent is one of the most significant public health challenges of this era. To date, the scientific community undoubtedly highlights mitochondrial dysfunction as a hallmark of cancer cells. Permeabilization of the mitochondrial membranes has been implicated as the most considerable footprint in apoptosis-mediated cancer cell death. Under the condition of mitochondrial calcium overload, exclusively mediated by oxidative stress, an opening of a nonspecific channel with a well-defined diameter in mitochondrial membrane allows free exchange between the mitochondrial matrix and the extra mitochondrial cytosol of solutes and proteins up to 1.5 kDa. Such a channel/nonspecific pore is recognized as the mitochondrial permeability transition pore (mPTP). mPTP has been established for regulating apoptosis-mediated cancer cell death. It has been evident that mPTP is critically linked with the glycolytic enzyme hexokinase II to defend cellular death and reduce cytochrome c release. However, elevated mitochondrial Ca2+ loading, oxidative stress, and mitochondrial depolarization are critical factors leading to mPTP opening/activation. Although the exact mechanism underlying mPTP-mediated cell death remains elusive, mPTP-mediated apoptosis machinery has been considered as an important clamp and plays a critical role in the pathogenesis of several types of cancers. In this review, we focus on structure and regulation of the mPTP complex-mediated apoptosis mechanisms and follow with a comprehensive discussion addressing the development of novel mPTP-targeting drugs/molecules in cancer treatment.
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DOI：
10.1177/1073274818804489
发表时间：
2018-01
期刊：
Cancer control : journal of the Moffitt Cancer Center
影响因子：
--
作者：
Du Y;Wu J;Luo L
通讯作者：
Luo L
影响因子：
3.7
作者：
Wang SY;Wei YH;Shieh DB;Lin LL;Cheng SP;Wang PW;Chuang JH
通讯作者：
Chuang JH
DOI：
10.4103/1793-5482.110274
发表时间：
2013-01
期刊：
Asian journal of neurosurgery
影响因子：
--
作者：
Venkataramanaa NK;Venkatesh PK;Dwarakanath BS;Vani S
通讯作者：
Vani S
影响因子：
--
作者：
Yin G;Fan J;Zhou W;Ding Q;Zhang J;Wu X;Tang P;Zhou H;Wan B;Yin G
通讯作者：
Yin G