Key Laboratory of Soft Matter Physics, Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12118-12123. doi: 10.1073/pnas.1810017115. Epub 2018 Nov 14.
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.
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学至关重要。细胞凋亡是一种程序性细胞死亡的过程,细胞形态和组织发生剧烈变化,在此过程中,信号分子在细胞内的不同细胞器之间运输。然而,细胞凋亡过程中细胞内运输如何变化尚不清楚。在这里,我们使用单颗粒跟踪方法研究了细胞内运输的动力学,发现早期凋亡细胞中内吞小泡的定向和扩散运动都加快了。通过仔细排除细胞内运输中涉及的其他因素,加速的原因归因于三磷酸腺苷 (ATP) 浓度的升高。更重要的是,我们表明,加速的细胞内运输对于细胞凋亡是至关重要的,并且当细胞内运输的动力学被调节回正常水平时,细胞凋亡被延迟。我们的结果表明了运输动力学在细胞凋亡中的重要作用,并从物理角度揭示了细胞凋亡的机制。