Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Crete, Greece.
Department of Biology, School of Sciences and Engineering, University of Crete, 71110 Heraklion, Crete, Greece.
Int J Mol Sci. 2023 Feb 20;24(4):4230. doi: 10.3390/ijms24044230.
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.
SNARE 蛋白位于相对的膜之间，促进囊泡融合，这是分泌、内吞和自噬等普遍生理过程所必需的。随着年龄的增长，神经分泌 SNARE 的活性下降，与年龄相关的神经紊乱有关。尽管 SNARE 复合物的组装和拆卸对于膜融合很重要，但它们的多样化定位阻碍了对其功能的全面理解。在这里，我们揭示了一组 SNARE 蛋白，即突触结合蛋白 SYX-17、突触小泡相关蛋白 VAMP-7、SNB-6 和连接因子 USO-1，它们在体内要么定位于线粒体附近，要么与线粒体接近。我们将它们称为线粒体 SNARE，并表明缺乏线粒体 SNARE 的动物表现出线粒体质量增加和自噬体积累。SNARE 拆卸因子 NSF-1 似乎是线粒体 SNARE 耗竭效应所必需的。此外，我们发现线粒体 SNARE 在神经元和非神经元组织的正常衰老中都是不可或缺的。总的来说，我们发现了一组以前未被识别的 SNARE 蛋白，它们定位于线粒体，并提出了线粒体 SNARE 组装和拆卸因子在基础自噬调节和衰老中的作用。
