title: Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system.
abstract: Mitochondria are considered autonomous organelles, physically separated from endocytic and biosynthetic pathways. However, recent work uncovered a PINK1/parkin-dependent vesicle transport pathway wherein oxidized or damaged mitochondrial content are selectively delivered to the late endosome/lysosome for degradation, providing evidence that mitochondria are indeed integrated within the endomembrane system. Given that mitochondria have not been shown to use canonical soluble NSF attachment protein receptor (SNARE) machinery for fusion, the mechanism by which mitochondrial-derived vesicles (MDVs) are targeted to the endosomal compartment has remained unclear. In this study, we identify syntaxin-17 as a core mitochondrial SNARE required for the delivery of stress-induced PINK1/parkin-dependent MDVs to the late endosome/lysosome. Syntaxin-17 remains associated with mature MDVs and forms a ternary SNARE complex with SNAP29 and VAMP7 to mediate MDV-endolysosome fusion in a manner dependent on the homotypic fusion and vacuole protein sorting (HOPS) tethering complex. Syntaxin-17 can be traced to the last eukaryotic common ancestor, hinting that the removal of damaged mitochondrial content may represent one of the earliest vesicle transport routes in the cell.
authors.affiliation: McGill Parkinson Program, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada Neurodegenerative Diseases Group, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Gian-Luca
authors.initials: GL
authors.lastname: McLelland
authors.affiliation: McGill Parkinson Program, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada Neurodegenerative Diseases Group, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Sydney A
authors.identifier: 0000-0002-8591-2062
authors.initials: SA
authors.lastname: Lee
authors.affiliation: Rare Diseases Group, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada.
authors.forename: Heidi M
authors.identifier: 0000-0003-4666-2280
authors.initials: HM
authors.lastname: McBride
authors.affiliation: McGill Parkinson Program, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada Neurodegenerative Diseases Group, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada ted.fon@mcgill.ca.
authors.forename: Edward A
authors.identifier: 0000-0002-5520-6239
authors.initials: EA
authors.lastname: Fon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D008928:Mitochondria / Q000378:metabolism* / Q000648:ultrastructure; D063306:Mitophagy; D046912:Multiprotein Complexes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism*; D050600:SNARE Proteins / Q000737:chemistry / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D050765:Qa-SNARE Proteins; D050600:SNARE Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein