Mitochondria-Judges and Executioners of Cell Death Sentences.
Mitochondria-Judges and Executioners of Cell Death Sentences.
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DOI：
10.1016/j.molcel.2016.02.019
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发表时间：
2016-03-03
期刊：
影响因子：
16
通讯作者：
Letai A
中科院分区：
文献类型：
--
作者：
Bhola PD;Letai A
细胞凋亡是程序性细胞死亡的一种形式，对于人类基本发育和生理学至关重要。过去二十年细胞生物学中更重要的惊喜之一是线粒体在哺乳动物细胞中代表许多细胞凋亡诱导信号的物理汇聚点的程度。线粒体不仅决定细胞是否死亡，而且还释放有毒蛋白质，最终导致广泛的蛋白水解、核溶解和细胞吞噬。线粒体外膜上的 Bcl-2 家族蛋白之间的相互作用控制着这些有毒蛋白的释放，进而控制细胞凋亡。该途径与癌症治疗特别相关，因为大多数癌症化疗都会触发线粒体介导的细胞凋亡。在这篇综述中，我们讨论了 Bcl-2 家族相互作用的最新进展、上游因素对它们的控制，以及线粒体本身如何改变这些相互作用。我们还重点介绍了线粒体介导的细胞凋亡和利用该途径的新型癌症疗法的最新临床见解。线粒体根据许多生理和治疗刺激做出细胞死亡决定。在这篇综述中，我们重点介绍了线粒体和 Bcl-2 蛋白家族如何调节细胞死亡的开创性和最新进展。我们特别讨论了 Bcl-2 家族相互作用的最新进展、上游因素对它们的控制，以及线粒体本身如何改变这些相互作用。我们还重点介绍了线粒体介导的细胞凋亡以及如何利用该途径的癌症治疗的最新临床见解。
Apoptosis is a form of programmed cell death that is critical for basic human development and physiology. One of the more important surprises in cell biology in the last two decades is the extent to which mitochondria represent a physical point of convergence for many apoptosis inducing signals in mammalian cells. Mitochondria not only adjudicate the decision of whether or not to commit to cell death, but also release toxic proteins culminating in widespread proteolysis, nucleolysis, and cell engulfment. Interactions among Bcl-2 family proteins at the mitochondrial outer membrane controls the release of these toxic proteins, and by extension control cellular commitment to apoptosis. This pathway is particularly relevant to cancer treatment, as most cancer chemotherapies trigger mitochondrial mediated apoptosis. In this review, we discuss recent advances in the Bcl-2 family interactions, their control by upstream factors, and how the mitochondria itself alters these interactions. We also highlight recent clinical insights into mitochondrial mediated apoptosis and novel cancer therapies that exploit this pathway. Mitochondria adjudicate the cell death decision in response to many physiological and therapeutic stimuli. The review we highlight seminal and recent advances on how mitochondria and the Bcl-2 family of proteins regulate cell death. In particular we discuss recent advances in the Bcl-2 family interactions, their control by upstream factors, and how the mitochondria itself alters these interactions. We also highlight recent clinical insights into mitochondrial mediated apoptosis and how cancer therapies that exploit this pathway.