SNARE proteins reside between opposing membranes and facilitate vesicle fusion, a physiological process ubiquitously required for secretion, endocytosis and autophagy. With age, neurosecretory SNARE activity drops and is pertinent to age-associated neurological disorders. Despite the importance of SNARE complex assembly and disassembly in membrane fusion, their diverse localization hinders the complete understanding of their function. Here, we revealed a subset of SNARE proteins, the syntaxin SYX-17, the synaptobrevins VAMP-7, SNB-6 and the tethering factor USO-1, to be either localized or in close proximity to mitochondria, in vivo. We term them mitoSNAREs and show that animals deficient in mitoSNAREs exhibit increased mitochondria mass and accumulation of autophagosomes. The SNARE disassembly factor NSF-1 seems to be required for the effects of mitoSNARE depletion. Moreover, we find mitoSNAREs to be indispensable for normal aging in both neuronal and non-neuronal tissues. Overall, we uncover a previously unrecognized subset of SNAREs that localize to mitochondria and propose a role of mitoSNARE assembly and disassembly factors in basal autophagy regulation and aging.
机构:
Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Lapierre, Louis R.
Silvestrini, Melissa J.
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CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA
CUNY, Grad Ctr, New York, NY USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Silvestrini, Melissa J.
Nunez, Lizbeth
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CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Nunez, Lizbeth
Ames, Kristina
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CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA
CUNY, Grad Ctr, New York, NY USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Ames, Kristina
Wong, Sara
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CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Wong, Sara
Le, Thuc T.
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Nevada Canc Inst, Dept Drug Target & Discovery, Las Vegas, NV USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Le, Thuc T.
Hansen, Malene
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Sanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA
Hansen, Malene
Melendez, Alicia
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CUNY Queens Coll, Dept Biol, Flushing, NY 11367 USA
CUNY, Grad Ctr, New York, NY USASanford Burnham Med Res Inst, Del E Webb Neurosci Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA