IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer
IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer
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DOI：
10.1038/s41467-019-11646-3
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发表时间：
2019-08-19
影响因子：
16.6
通讯作者：
Hajnoczky, Gyorgy
中科院分区：
文献类型：
--
作者：
Bartok, Adam;Weaver, David;Hajnoczky, Gyorgy
内质网（ER）和线粒体的接触部位在IP3受体（IP3R）和线粒体钙单转运体之间局部传递钙信号，对细胞存活至关重要。目前尚不清楚IP3R是否也在接触形成中起结构作用，以及不同的IP3R异构体是否具有冗余功能。利用IP3R缺失细胞模型和一系列超分辨率和超微结构方法，我们证明IP3R是维持er-线粒体接触所必需的。这一作用与钙通量无关。我们还表明，虽然每种异构体都可以支持接触，但2型IP3R在将钙输送到线粒体方面是最有效的。因此，这些研究揭示了IP3R的非规范结构作用，并将注意力转向了之前在er线粒体钙信号传导中被忽视的2型IP3R。
Contact sites of endoplasmic reticulum (ER) and mitochondria locally convey calcium signals between the IP3 receptors (IP3R) and the mitochondrial calcium uniporter, and are central to cell survival. It remains unclear whether IP3Rs also have a structural role in contact formation and whether the different IP3R isoforms have redundant functions. Using an IP3R-deficient cell model rescued with each of the three IP3R isoforms and an array of super-resolution and ultrastructural approaches we demonstrate that IP3Rs are required for maintaining ER-mitochondrial contacts. This role is independent of calcium fluxes. We also show that, while each isoform can support contacts, type 2 IP3R is the most effective in delivering calcium to the mitochondria. Thus, these studies reveal a non-canonical, structural role for the IP3Rs and direct attention towards the type 2 IP3R that was previously neglected in the context of ER-mitochondrial calcium signaling.