RRC ID 34897
Author Arasaki K, Shimizu H, Mogari H, Nishida N, Hirota N, Furuno A, Kudo Y, Baba M, Baba N, Cheng J, Fujimoto T, Ishihara N, Ortiz-Sandoval C, Barlow LD, Raturi A, Dohmae N, Wakana Y, Inoue H, Tani K, Dacks JB, Simmen T, Tagaya M.
Title A role for the ancient SNARE syntaxin 17 in regulating mitochondrial division.
Journal Dev. Cell
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.
Volume 32(3)
Pages 304-17
Published 2015-2-9
DOI 10.1016/j.devcel.2014.12.011
PII S1534-5807(14)00808-9
PMID 25619926
MeSH Endoplasmic Reticulum / metabolism* GTP Phosphohydrolases / metabolism HeLa Cells Humans Mitochondria / metabolism* Mitochondrial Dynamics / physiology* Mitochondrial Proteins / metabolism Phagosomes / metabolism Qa-SNARE Proteins / metabolism*
IF 9.616
Times Cited 16
WOS Category DEVELOPMENTAL BIOLOGY CELL BIOLOGY
Resource
DNA material FLAG-STX17 WT (RDB13258) FLAG-STX17 K254C (RDB13259).