BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites
BAP31 regulates mitochondrial function via interaction with Tom40 within ER-mitochondria contact sites
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DOI：
10.1126/sciadv.aaw1386
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发表时间：
2019-06-01
期刊：
影响因子：
13.6
通讯作者：
Namba, Takushi
中科院分区：
文献类型：
--
作者：
Namba, Takushi
内质网（ER）是由大的膜结合区室，其膜子域似乎是在密切接触线粒体通过ER-线粒体接触网站。在这里，我证明了ER膜蛋白，BAP 31，作为一个关键因素，在线粒体内稳态刺激的构成的线粒体复合物I通过形成一个ER-线粒体桥接蛋白复合物。在该复合物中，BAP 31与包括Tom 40在内的位于线粒体内的蛋白质相互作用，以刺激NDUFS 4（复合物I的组分）从细胞质到线粒体的易位。BAP 31-Tom 40复合物的破坏通过减少NDUFS 4定位于线粒体来抑制线粒体复合物I活性和氧消耗。因此，BAP 31-Tom 40 ER-线粒体桥接复合物介导线粒体功能的调节，并作为先前未鉴定的应激传感器发挥作用，代表了通过这些细胞器之间的接触位点建立ER-线粒体通信的机制。
The endoplasmic reticulum (ER) is composed of large membrane-bound compartments, and its membrane subdomain appears to be in close contact with mitochondria via ER-mitochondria contact sites. Here, I demonstrate that the ER membrane protein, BAP31, acts as a key factor in mitochondrial homeostasis to stimulate the constitution of the mitochondrial complex I by forming an ER-mitochondria bridging protein complex. Within this complex, BAP31 interacts with mitochondria-localized proteins, including Tom40, to stimulate the translocation of NDUFS4, the component of complex I from the cytosol to the mitochondria. Disruption of the BAP31-Tom40 complex inhibits mitochondrial complex I activity and oxygen consumption by the decreased NDUFS4 localization to the mitochondria. Thus, the BAP31-Tom40 ER-mitochondria bridging complex mediates the regulation of mitochondrial function and plays a role as a previously unidentified stress sensor, representing a mechanism for the establishment of ER-mitochondria communication via contact sites between these organelles.