Intracellular transport is accelerated in early apoptotic cells
Intracellular transport is accelerated in early apoptotic cells
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早期凋亡细胞的细胞内运输加速
DOI：
10.1073/pnas.1810017115
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发表时间：
2018-11-27
影响因子：
11.1
通讯作者：
Li, Hui
中科院分区：
文献类型：
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作者：
Li, Bo;Dou, Shuo-Xing;Li, Hui
意义：细胞凋亡是一种程序性细胞死亡，对胚胎发育、机体内环境平衡甚至癌症至关重要。尽管在过去的40年里，人们对细胞凋亡的生物学方面如分子信号通路和细胞结构转化进行了深入的研究，但对细胞内动力学等物理方面的研究仍然很少。我们报道，在早期的凋亡细胞中，定向和非定向运动的细胞内转运都被加速，这是由于胞内ATP水平升高所致。此外，我们发现，通过调节加速的细胞内转运回到正常水平，细胞凋亡的进程显著延迟。这项研究从物理角度强调了细胞内转运动力学在细胞凋亡中的重要作用。细胞内蛋白质和细胞器的运输对于建立和维持细胞内组织和细胞生理至关重要。细胞凋亡是细胞形态和组织发生显著变化的细胞程序性死亡过程，在此过程中信号分子在细胞内的不同细胞器之间进行运输。然而，细胞内转运如何在细胞凋亡过程中发生变化仍是个未知数。在这里，我们利用单粒子跟踪方法研究细胞内转运的动力学，发现在早期凋亡的细胞中，内吞液泡的定向运动和扩散运动都被加速。在仔细排除参与细胞内转运的其他因素后，加速的原因被归因于三磷酸腺苷(ATP)浓度的提高。更重要的是，我们发现加速的细胞内转运是细胞凋亡的关键，当细胞内转运的动力学被调节到正常水平时，细胞凋亡被延迟。我们的结果证明了转运动力学在细胞凋亡中的重要作用，并从物理角度阐明了细胞凋亡的机制。
Significance Apoptosis is a programmed cell death and critical to embryonic development, organism homeostasis, and even cancer. Although the biological aspects of apoptosis such as the molecular signaling pathway and cellular structure transformation have been intensively studied over the past 40 years, studies of the physical aspects such as intracellular dynamics are still lacking. We report that the intracellular transport with both directed and nondirected motions is accelerated in early apoptotic cells, and this results from an elevated cytosolic ATP level. Furthermore, we find that, by regulating the accelerated intracellular transport back to the normal level, the apoptotic progress is significantly delayed. This study, from the physical perspective, highlights the critical importance of intracellular transport dynamics in apoptosis. Intracellular transport of cellular proteins and organelles is critical for establishing and maintaining intracellular organization and cell physiology. Apoptosis is a process of programmed cell death with dramatic changes in cell morphology and organization, during which signaling molecules are transported between different organelles within the cells. However, how the intracellular transport changes in cells undergoing apoptosis remains unknown. Here, we study the dynamics of intracellular transport by using the single-particle tracking method and find that both directed and diffusive motions of endocytic vesicles are accelerated in early apoptotic cells. With careful elimination of other factors involved in the intracellular transport, the reason for the acceleration is attributed to the elevation of adenosine triphosphate (ATP) concentration. More importantly, we show that the accelerated intracellular transport is critical for apoptosis, and apoptosis is delayed when the dynamics of intracellular transport is regulated back to the normal level. Our results demonstrate the important role of transport dynamics in apoptosis and shed light on the apoptosis mechanism from a physical perspective.