Gasdermins in Apoptosis: New players in an Old Game
Gasdermins in Apoptosis: New players in an Old Game
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发表时间：
2019-12
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通讯作者：
Corey Rogers;E. Alnemri
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作者：
Corey Rogers;E. Alnemri
细胞凋亡是程序性细胞死亡（PCD）的一种形式，其在去除不需要的或威胁宿主生物体健康的多余或危险的细胞群体中发挥关键的生理作用。虽然在20世纪70年代开始，导致细胞凋亡程序激活的分子途径已经被广泛研究和表征，但新的证据表明，gasdermin超家族的成员是新的成孔蛋白，其通过透化线粒体来增加细胞凋亡，并通过诱导继发性坏死/焦亡来参与细胞凋亡程序的最后阶段。这些发现可以解释该领域的突出问题，例如为什么某些gasdermin成员使细胞对凋亡敏感，以及为什么一些凋亡细胞也显示出坏死的形态学特征。此外，gasdermins和细胞凋亡之间的相互作用也可以解释为什么这些基因的遗传和表观遗传改变会导致癌症和听力损失等疾病和障碍。本文综述了我们目前对几个gasdermin超家族成员的功能的了解，他们在细胞凋亡中的作用，以及他们如何可能有助于病理生理条件。
Apoptosis is a form of programmed cell death (PCD) that plays critical physiological roles in removing superfluous or dangerous cell populations that are unneeded or threatening to the health of the host organism. Although the molecular pathways leading to activation of the apoptotic program have been extensively studied and characterized starting in the 1970s, new evidence suggests that members of the gasdermin superfamily are novel pore-forming proteins that augment apoptosis by permeabilizing the mitochondria and participate in the final stages of the apoptotic program by inducing secondary necrosis/pyroptosis. These findings may explain outstanding questions in the field such as why certain gasdermin members sensitize cells to apoptosis, and why some apoptotic cells also show morphological features of necrosis. Furthermore, the interplay between the gasdermins and apoptosis may also explain why genetic and epigenetic alterations in these genes cause diseases and disorders like cancer and hearing loss. This review focuses on our current understanding of the function of several gasdermin superfamily members, their role in apoptosis, and how they may contribute to pathophysiological conditions.