In Smooth Muscle, Mitochondrial Movement is Restricted in Native Cells and Unrestricted and Trafficked When Cells are in Culture

In Smooth Muscle, Mitochondrial Movement is Restricted in Native Cells and Unrestricted and Trafficked When Cells are in Culture
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在平滑肌中,线粒体运动在天然细胞中受到限制,而当细胞处于培养状态时则不受限制和运输

DOI:
10.1016/j.bpj.2009.12.1617
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发表时间:
2010
影响因子:
3.4
通讯作者:
Chalmers S
Chalmers S
中科院分区:
生物学3区
文献类型:
--
作者:
Chalmers S

文献摘要

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线粒体在细胞中的定位对于局部提供ATP、调节[Ca2+]c信号、脂质和活性氧物种的产生、氧化还原控制和启动细胞死亡信号是重要的。在平滑肌中,线粒体的钙摄取通过IP-3R促进肌浆网钙的释放,这表明从IP-3R胞浆表面局部地去除了离子,从而维持了通道活性1。然而,这种关系所暗示的密切的物理相互作用与已报道的线粒体在整个胞浆中的自由运动是不相容的。在这里,基于图像相关的单颗粒追踪的线粒体新鲜分离的单个豚鼠结肠平滑肌细胞,显示线粒体表现出非常有限的运动。检测到线粒体的布朗运动,但没有随着时间的推移产生细胞器的任何显着移位。肌动蛋白解聚剂Latrunculin B(10μM)和微管阻断剂诺康唑(10μM)都不能增加线粒体的运动。相反,当新鲜分离的平滑肌细胞在细胞培养条件下保持14天时,线粒体的运动性显著增加。线粒体呈现快速定向运动,随着时间的推移,布朗运动导致线粒体移位。这些结果表明,在新鲜分离的平滑肌细胞中,线粒体要么受到限制,要么被拴住以限制运动;而当相同的细胞在培养中分裂和增殖时,这些限制失去了,线粒体呈现随机行走的扩散运动,并可进入细胞内的运输机制。
Positioning of mitochondria in the cell is important for the local provision of ATP and for regulation of [Ca 2+] c signals, lipid and reactive oxygen species production, redox control and initiation of cell death signals. In smooth muscle, mitochondrial Ca 2+ uptake promotes Ca 2+ release from the sarcoplasmic reticulum via by IP 3 R, suggesting a localised removal of the ion from the IP 3 R cytosolic face that maintains channel activity 1. The close physical interaction that this relationship implies is not compatible, however, with the reported free movement of mitochondria throughout the cytosol. Here, image correlation based single particle tracking of mitochondria in freshly-isolated single smooth muscle cells from guinea-pig colon, shows that mitochondria displayed very limited movement. Brownian motion of mitochondria was detected but did not generate any significant displacement of the organelle over time. Neither the actin depolymerising agent latrunculin B (10 μM), nor the microtubule disrupter nocodazole (10 μM) increased mitochondrial movement. In contrast, when freshly-isolated smooth muscle cells were maintained in cell culture conditions for 14 days mitochondrial motility was substantially increased. Mitochondria displayed rapid, directed motion and Brownian movement resulted in displacement of the mitochondria over time. These results suggest that in freshly-isolated smooth muscle cells, mitochondria are either confined or tethered to limit movement; whereas when the same cells divide and proliferate in culture these restraints are lost, mitochondria display random-walk diffusive motion and are accessible to the intracellular trafficking machinery.