Mitochondrial dynamics as regulators of cancer biology.
Mitochondrial dynamics as regulators of cancer biology.
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DOI：
10.1007/s00018-016-2451-3
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Chipuk JE
中科院分区：
文献类型：
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作者：
Trotta AP;Chipuk JE
线粒体是动态细胞器，其提供驱动关键细胞过程（例如存活、增殖和迁移）所需的能量。所有这些过程的关键是线粒体结构的变化，这是一种包括线粒体网络融合和分裂（裂变）的机械机制。线粒体形状、大小和定位的变化以受调节的方式发生，以维持能量和代谢稳态，而线粒体动力学的失调与代谢功能障碍和疾病的发作相关。在癌症中，驱动过度增殖、增加细胞内压力和限制营养供应的致癌信号都能够改变癌细胞的生物能量和生物合成需求。因此，线粒体的功能和形状迅速适应这些不利的条件，以支持癌细胞增殖和逃避细胞死亡程序的激活。在这篇综述中，我们将讨论线粒体动力学的分子机制，并将最近的见解整合到线粒体形状的变化如何影响细胞迁移，分化，凋亡和新的靶向癌症治疗的发展机会。
Mitochondria are dynamic organelles that supply energy required to drive key cellular processes, such as survival, proliferation, and migration. Critical to all of these processes are changes in mitochondrial architecture, a mechanical mechanism encompassing both fusion and fragmentation (fission) of the mitochondrial network. Changes to mitochondrial shape, size, and localization occur in a regulated manner in order to maintain energy and metabolic homeostasis, while deregulation of mitochondrial dynamics is associated with the onset of metabolic dysfunction and disease. In cancers, oncogenic signals that drive excessive proliferation, increase intracellular stress, and limit nutrient supply are all able to alter the bioenergetic and biosynthetic requirements of cancer cells. Consequently, mitochondrial function and shape rapidly adapt to these hostile conditions in order to support cancer cell proliferation and evade activation of cell death programs. In this review we will discuss the molecular mechanisms governing mitochondrial dynamics and integrate recent insights into how changes in mitochondrial shape affect cellular migration, differentiation, apoptosis, and opportunities for the development of novel targeted cancer therapies.