title: A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division.
abstract: 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 Ca(2+) homeostasis and interferes with Rab32-mediated regulation of mitochondrial 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.
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Arasaki
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mogari
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nishida
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Hirota
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuno
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kudo
authors.affiliation: Research Institute for Science and Technology, Kogakuin University, Hachioji, Tokyo 192-0015, Japan; Informatics Program, Graduate School of Engineering, Kogakuin University, Hachioji, Tokyo 192-0015, Japan.
authors.forename: Misuzu
authors.initials: M
authors.lastname: Baba
authors.affiliation: Informatics Program, Graduate School of Engineering, Kogakuin University, Hachioji, Tokyo 192-0015, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Baba
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
authors.affiliation: Department of Protein Biochemistry, Institute of Life Science, Kurume University, Kurume, Fukuoka 839-0864, Japan.
authors.forename: Naotada
authors.initials: N
authors.lastname: Ishihara
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Carolina
authors.initials: C
authors.lastname: Ortiz-Sandoval
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Lael D
authors.initials: LD
authors.lastname: Barlow
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Arun
authors.initials: A
authors.lastname: Raturi
authors.affiliation: Biomolecular Characterization Team, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakana
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inoue
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Tani
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmen
authors.affiliation: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: tagaya@toyaku.ac.jp.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Tagaya
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D063154:Mitochondrial Dynamics / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; D050765:Qa-SNARE Proteins; D020558:GTP Phosphohydrolases