A Role for the Ancient SNARE Syntaxin 17 in Regulating Mitochondrial Division

被引:149
作者
Arasaki, Kohei [1 ]
Shimizu, Hiroaki [1 ]
Mogari, Hirofumi [1 ]
Nishida, Naoki [1 ]
Hirota, Naohiko [1 ]
Furuno, Akiko [1 ]
Kudo, Yoshihisa [1 ]
Baba, Misuzu [2 ,3 ]
Baba, Norio [3 ]
Cheng, Jinglei [4 ]
Fujimoto, Toyoshi [4 ]
Ishihara, Naotada [5 ]
Ortiz-Sandoval, Carolina [6 ]
Barlow, Lael D. [6 ]
Raturi, Arun [6 ]
Dohmae, Naoshi [7 ]
Wakana, Yuichi [1 ]
Inoue, Hiroki [1 ]
Tani, Katsuko [1 ]
Dacks, Joel B. [6 ]
Simmen, Thomas [6 ]
Tagaya, Mitsuo [1 ]
机构
[1] Tokyo Univ Pharm & Life Sci, Sch Life Sci, Hachioji, Tokyo 1920392, Japan
[2] Kogakuin Univ, Sci & Technol Res Inst, Hachioji, Tokyo 1920015, Japan
[3] Kogakuin Univ, Grad Sch Engn, Informat Program, Hachioji, Tokyo 1920015, Japan
[4] Nagoya Univ, Grad Sch Med, Dept Anat & Mol Cell Biol, Nagoya, Aichi 4668550, Japan
[5] Kurume Univ, Inst Life Sci, Dept Prot Biochem, Kurume, Fukuoka 8390864, Japan
[6] Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada
[7] RIKEN, Biomol Characterizat Team, Wako, Saitama 3510198, Japan
基金
加拿大自然科学与工程研究理事会;
关键词
ENDOPLASMIC-RETICULUM; MEMBRANE MAM; ER MEMBRANES; FUSION; FISSION; APOPTOSIS; DYNAMICS; AUTOPHAGOSOMES; DEGRADATION; STRESS;
D O I
10.1016/j.devcel.2014.12.011
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
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.
引用
收藏
页码:304 / 317
页数:14
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