期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 24, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/ijms24044230
关键词
mitochondria; SNAREs; autophagy; aging; SYX-17; NSF-1
SNARE proteins are involved in vesicle fusion and play a crucial role in secretion, endocytosis, and autophagy. Deficiency of certain SNARE proteins, which localize to or in close proximity to mitochondria, leads to increased mitochondrial mass and autophagosome accumulation. These mitoSNARE proteins are essential for normal aging in both neuronal and non-neuronal tissues. The findings suggest a role of mitoSNARE assembly and disassembly in the regulation of autophagy and aging.
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.
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