Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthetic NHK1 Peptides
2.2. Cell Cultures, Mantainance, and Viability
2.3. Membrane Permeability Assay by Transwell System
2.4. Fluorescence Mycroscopy
2.5. High-Resolution Respirometry
2.6. Analysis of Respirometric States
2.7. Cell Lysates and Fractionation
2.8. Western Blot Analysis
2.9. Real-Time PCR
2.10. Flow Cytometry Experiments
2.11. Cell Transfection
2.12. Pull-Down Assay
2.13. Docking Simulation
2.14. Statistical Analysis
3. Results
3.1. Assessment of Membrane Permeability to NHK1 Peptide
3.2. NHK1 Ameliorates Cell Viability and Oxygen Consumption in NSC34-SOD1G93A Cells
3.3. NHKI Peptide Improves ATP-Linked OXPHOS Flows but Not Complex I Activity
3.4. NHK1 Peptide Increases VDAC1 Levels While Reduces SOD1 G93A Mitochondrial Accumulation
3.5. VDAC1 Overexpression Is Not Sufficient to Counteract SOD1 G93A Toxicity
3.6. NHK1 Peptide Interacts with VDAC1
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALS | amyotrophic lateral sclerosis |
DOXY | doxycycline |
ET | electron transport |
FCR(s) | flux control ratio(s) |
FITC | fluoresceine isothiocyanate |
FSEC | fluorescence-detection size-exclusion chromatography |
HK | hexokinase |
HRR | high-resolution respirometry |
MAMs | mitochondrial-associated membranes |
MN(s) | motor neuron(s) |
OMM | outer mitochondrial membrane |
SOD1 | Cu/Zn superoxide dismutase |
VDAC | voltage-dependent anion channel |
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Magrì, A.; Risiglione, P.; Caccamo, A.; Formicola, B.; Tomasello, M.F.; Arrigoni, C.; Zimbone, S.; Guarino, F.; Re, F.; Messina, A. Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration. Biomedicines 2021, 9, 948. https://doi.org/10.3390/biomedicines9080948
Magrì A, Risiglione P, Caccamo A, Formicola B, Tomasello MF, Arrigoni C, Zimbone S, Guarino F, Re F, Messina A. Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration. Biomedicines. 2021; 9(8):948. https://doi.org/10.3390/biomedicines9080948
Chicago/Turabian StyleMagrì, Andrea, Pierpaolo Risiglione, Antonella Caccamo, Beatrice Formicola, Marianna Flora Tomasello, Cristina Arrigoni, Stefania Zimbone, Francesca Guarino, Francesca Re, and Angela Messina. 2021. "Small Hexokinase 1 Peptide against Toxic SOD1 G93A Mitochondrial Accumulation in ALS Rescues the ATP-Related Respiration" Biomedicines 9, no. 8: 948. https://doi.org/10.3390/biomedicines9080948