6533b836fe1ef96bd12a13cf
RESEARCH PRODUCT
Synaptosomes: new vesicles for neuronal mitochondrial transplantation
Gaetana PorcelliGiacoma GalizziCeleste Caruso BavisottoDomenico NuzzoMarta Di CarloPasquale Massimo PiconeDonatella BulonePier Luigi San Biagiosubject
MaleFIS1Mitochondrial DNAlcsh:Medical technologylcsh:BiotechnologyBiomedical EngineeringPharmaceutical ScienceMedicine (miscellaneous)BioengineeringMitochondrionDNA MitochondrialApplied Microbiology and BiotechnologyMembrane Potentials03 medical and health sciencesDrug Delivery Systems0302 clinical medicinelcsh:TP248.13-248.65medicineAnimalsHomeostasisProtein Interaction Domains and MotifsNeurodegenerationDelivery system030304 developmental biologyMitochondrial transplantationSynaptosome0303 health sciencesbiologyChemistryResearchCytochrome cNeurodegenerationSynaptosomes Mitochondria Neurodegeneration Delivery system Mitochondrial transplantationCytochromes cmedicine.diseaseRatsCell biologyMitochondriaTransplantationlcsh:R855-855.5Cytoplasmbiology.proteinMolecular Medicine030217 neurology & neurosurgerySubcellular FractionsSynaptosomesdescription
Abstract Background Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, a subcellular fraction of isolated synaptic terminal that contains mitochondria, as mitochondrial delivery systems. Results Synaptosome preparation was validated by the presence of Synaptophysin and PSD95. Synaptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/ml. Nile Red or CTX-FITCH labeled synaptosomes were internalized in LAN5 recipient cells by a mechanism involving specific protein–protein interaction, as demonstrated by loss of fusion ability after trypsin treatment and using different cell lines. The loading and release ability of the synaptosomes was proved by the presence of curcumin both into synaptosomes and LAN5 cells. The vitality of mitochondria transferred by Synaptosomes was demonstrated by the presence of Opa1, Fis1 and TOM40 mitochondrial proteins and JC-1 measurements. Further, synaptosomes deliver vital mitochondria into the cytoplasm of neuronal cells as demonstrated by microscopic images, increase of TOM 40, cytochrome c, Hexokinase II mitochondrial proteins, and presence of rat mitochondrial DNA. Finally, by using synaptosomes as a vehicle, healthy mitochondria restored mitochondrial function in cells containing rotenone or CCCp damaged mitochondria. Conclusions Taken together these results suggest that synaptosomes can be a natural vehicle for the delivery of molecules and organelles to neuronal cells. Further, the replacement of affected mitochondria with healthy ones could be a potential therapy for treating neuronal mitochondrial dysfunction-related diseases.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-01-01 |