MitoSNARE Assembly and Disassembly Factors Regulate Basal Autophagy and Aging in C. elegans

Ilias Gkikas; Ioanna Daskalaki; Konstantinos Kounakis; Nektarios Tavernarakis; Eirini Lionaki

doi:10.3390/ijms24044230

MitoSNARE Assembly and Disassembly Factors Regulate Basal Autophagy and Aging in C. elegans

Int J Mol Sci. 2023 Feb 20;24(4):4230. doi: 10.3390/ijms24044230.

Authors

Ilias Gkikas^{1

2}, Ioanna Daskalaki^{1

2}, Konstantinos Kounakis^{1

3}, Nektarios Tavernarakis^{1

3}, Eirini Lionaki¹

Affiliations

¹ Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas, 70013 Heraklion, Crete, Greece.
² Department of Biology, School of Sciences and Engineering, University of Crete, 71110 Heraklion, Crete, Greece.
³ Department of Basic Sciences, Faculty of Medicine, University of Crete, 71110 Heraklion, Crete, Greece.

Abstract

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.

Keywords: NSF-1; SNAREs; SYX-17; aging; autophagy; mitochondria.

MeSH terms

Aging*
Animals
Autophagy*
Caenorhabditis elegans* / physiology
Endocytosis
Membrane Fusion
SNARE Proteins* / physiology

Substances

SNARE Proteins

Grants and funding

This work was supported by the European Union Horizon 2020 FETOPEN, project “Dynamic”, under the grant agreement “GA-863203”, the European Research Council, under grant agreement “ERC-GA695190-MANNA” to N.T., the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT), under grant agreement No [1898] and No [2040] to E.L.