Kato Shun, Tagaya Mitsuo
School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji,Tokyo 192-0392, Japan.
Autophagy Rep. 2022 Mar 22;1(1):14-16. doi: 10.1080/27694127.2022.2033056. eCollection 2022.
Mammalian STX17 (syntaxin 17) plays different cellular roles, including in mitochondrial fission, lipid droplet expansion and macroautophagy/autophagy, depending on the nutritional status. STX17 has a long C-terminal hydrophobic domain (CHD) with a hairpin-like structure, flanked by a basic amino acid-enriched C-terminal tail (C-tail). STX17 is present in a wide variety of eukaryotes, but has been lost in several lineages during evolution. Moreover, the structure of its C-tail remarkably varies, although the CHD is highly conserved. Recently, we compared the localization and function of fly and nematode Syx17/SYX-17 proteins expressed in mammalian cells with that of human STX17. Fly Syx17 expressed in mammalian cells localizes almost exclusively to the cytosol and translocates to autophagosomes upon starvation, whereas nematode SYX-17 is mainly distributed to mitochondria and promotes mitochondrial fission, but does not participate in autophagy. In vivo experiments showed that fly and nematode STX17 homologs are not involved in mitochondrial fission and autophagy, respectively. These results provide important insights into the localization and function of STX17, which acts as a molecular sensor for different nutritional conditions.
哺乳动物的STX17（ syntaxin 17）根据营养状况发挥不同的细胞作用，包括参与线粒体分裂、脂滴扩张和巨自噬/自噬。STX17具有一个长的C末端疏水结构域（CHD），呈发夹样结构，两侧是富含碱性氨基酸的C末端尾巴（C尾）。STX17存在于多种真核生物中，但在进化过程中的几个谱系中已经丢失。此外，尽管CHD高度保守，但其C尾的结构却有显著差异。最近，我们将在哺乳动物细胞中表达的果蝇和线虫的Syx17/SYX - 17蛋白的定位和功能与人类STX17的进行了比较。在哺乳动物细胞中表达的果蝇Syx17几乎完全定位于细胞质，饥饿时转移至自噬体，而线虫SYX - 17主要分布于线粒体并促进线粒体分裂，但不参与自噬。体内实验表明，果蝇和线虫的STX17同源物分别不参与线粒体分裂和自噬。这些结果为STX17的定位和功能提供了重要见解，STX17可作为不同营养条件的分子传感器。
