Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells
Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells
复制标题
DOI：
10.1242/jcs.228544
复制
发表时间：
2019-05-01
影响因子：
4
通讯作者：
Idevall-Hagren, Olof
中科院分区：
文献类型：
--
作者：
Griesche, Nadine;Sanchez, Gonzalo;Idevall-Hagren, Olof
线粒体通过提供膜去极化所需的ATP在调节β细胞的胰岛素分泌中发挥重要作用，膜去极化导致电压依赖性Ca2+内流和随后的胰岛素颗粒胞吐。反过来，Ca2+也被线粒体迅速吸收，并对代谢发挥重要的反馈调节作用。本研究的目的是确定β细胞内线粒体的分布对这些细胞的分泌能力是否重要。我们发现，在啮齿动物β细胞中，皮质定位的线粒体丰富，并且这些线粒体在去极化后向细胞内部重新分布。再分配需要Ca2+诱导的皮层f -肌动蛋白网络的重塑。使用光调节的运动蛋白，我们将线粒体的皮质密度增加了两倍，并发现这减弱了电压依赖性的细胞质Ca2+浓度的增加，并抑制了胰岛素分泌。线粒体分布的活性依赖性变化可能对有效释放胰岛素颗粒所需的Ca2+微域的产生很重要。
Mitochondria play an essential role in regulating insulin secretion from beta cells by providing the ATP needed for the membrane depolarization that results in voltage-dependent Ca2+ influx and subsequent insulin granule exocytosis. Ca2+, in turn, is also rapidly taken up by the mitochondria and exerts important feedback regulation of metabolism. The aim of this study was to determine whether the distribution of mitochondria within beta cells is important for the secretory capacity of these cells. We find that cortically localized mitochondria are abundant in rodent beta cells, and that these mitochondria redistribute towards the cell interior following depolarization. The redistribution requires Ca2+-induced remodeling of the cortical F-actin network. Using light-regulated motor proteins, we increased the cortical density of mitochondria twofold and found that this blunted the voltage-dependent increase in cytosolic Ca2+ concentration and suppressed insulin secretion. The activity-dependent changes in mitochondria distribution are likely to be important for the generation of Ca2+ microdomains required for efficient insulin granule release.