A Role for the Ancient SNARE Syntaxin 17 in Regulating Mitochondrial Division
A Role for the Ancient SNARE Syntaxin 17 in Regulating Mitochondrial Division
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DOI：
10.1016/j.devcel.2014.12.011
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发表时间：
2015-02-09
影响因子：
11.8
通讯作者：
Tagaya, Mitsuo
中科院分区：
文献类型：
--
作者：
Arasaki, Kohei;Shimizu, Hiroaki;Tagaya, Mitsuo
最近的证据表明，内质网（ER）小管标志着GTdR Drp 1通过一种很大程度上未知的机制促进线粒体分裂的位点。在这里，我们表明，SNARE蛋白syntaxin 17（Syn 17）是存在于筏状结构的ER-线粒体接触位点，并通过确定Drp 1的定位和活性促进线粒体分裂。发夹样C-末端疏水结构域，包括Lys-254，但不是SNARE结构域，对于这种调节是重要的。Syn 17还调节ER Ca 2+稳态并干扰Rab 32介导的线粒体调节！动力学饥饿破坏了Syn 17-Drp 1的相互作用，从而有利于自噬过程中的线粒体伸长。因为我们还证明了Syn 17是一个古老的陷阱，我们的研究结果表明，Syn 17是最后一个真核生物共同祖先中ER-线粒体接触位点的原始关键调节因子之一。因此，Syn 17充当响应营养条件的开关，并将ER和自噬体的功能与线粒体动力学整合在一起。
Recent evidence suggests that endoplasmic reticulum (ER) tubules mark the sites where the GTPase Drp1 promotes mitochondrial fission via a largely unknown mechanism. Here, we show that the SNARE protein syntaxin 17 (Syn17) is present on raft-like structures of ER-mitochondria contact sites and promotes mitochondrial fission by determining Drp1 localization and activity. The hairpin-like C-terminal hydrophobic domain, including Lys-254, but not the SNARE domain, is important for this regulation. Syn17 also regulates ER Ca2+ homeostasis and interferes with Rab32-mediated regulation of mitochondria! dynamics. Starvation disrupts the Syn17-Drp1 interaction, thus favoring mitochondrial elongation during autophagy. Because we also demonstrate that Syn17 is an ancient SNARE, our findings suggest that Syn17 is one of the original key regulators for ER-mitochondria contact sites present in the last eukaryotic common ancestor. As such, Syn17 acts as a switch that responds to nutrient conditions and integrates functions for the ER and autophagosomes with mitochondrial dynamics.