Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells?
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture
2.2. Determination of Cell Viability by the MTT Assay
2.3. Determination of Mitochondrial Respiration Parameters
2.4. Determination of Protein Concentration
2.5. Determination of ATP Levels
2.6. Determination of Mitochondrial OXPHOS Complex I Enzymatic Activity
2.7. Western Blotting
2.8. Statistical Analysis
3. Results
4. Discussion
5. Limitations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Drug Parameters | vs. Control | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Lithium 24 hrs | Trehalose 24 hrs | Rapamycin 24 hrs | Resveratrol 24 hrs | NAC 24 hrs | Mn-Tbap 24 hrs | Lithium 48 hrs | Trehalose 48 hrs | Rapamycin 48 hrs | Resveratrol 48 hrs | NAC 48 hrs | Mn-Tbap 48 hrs | ||
Cell viability | MTT assay | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↑ |
ApoLive-Glo multiplex assay | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↑ | ↑ | ↔ | |
Mito. characteristics | Mito. mass | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ |
MMP (ΔψM) | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
ROS | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Mito. respiration | Basal OCR | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↓ | ↔ | ↔ | ↓ | ↔ | ↓ |
Proton leak | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↓ | ↔ | ↔ | ↓ | |
Maximal respiration | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↓ | |
Spare respiratory capacity | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↓ | |
ATP-linked OCR | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↓ | ↔ | ↓ | |
Non mito. respiration | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↑ | |
ATP | Levels | ↔ | ↑ | ↔ | ↓ | ↑ | ↔ | ↔ | ↑ | ↑ | ↑ | ↔ | ↑ |
Autophagy markers | LC3-II | ↑ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
p62 | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Complex I | Activity | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
Protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Mito. Complexes II-V | CoII protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
CoIII protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ | |
CoIV protein levels | ↔ | ↑ | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
CoV protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
Drug Parameters | vs. Control | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Rot. for 72 hrs | Rot.+Li. Last 24 hrs | Rot.+Tre. Last 24 hrs | Rot.+Rap. Last 24 hrs | Rot.+Res. Last 24 hrs | Rot.+NAC Last 24 hrs | Rot.+Mn. Last 24 hrs | Rot. for 96 hrs | Rot.+Li. Last 48 hrs | Rot.+Tre. Last 48 hrs | Rot.+Rap. Last 48 hrs | Rot.+Res. Last 48 hrs | Rot.+NAC Last 48 hrs | Rot.+Mn. Last 48 hrs | ||
Cell viability | MTT assay | ↔ | ↔ | ↓ | ↔ | ↓ | ↔ | ↓ | ↔ | ↑ | ↔ | ↓ | ↓ | ↑ | ↓ |
ApoLive-Glo multiplex assay | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Mito. Characteristics | Mito. mass | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ |
MMP (ΔψM) | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
ROS | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Mito. respiration | Basal OCR | ↑ | ↔ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ |
Proton leak | ↑ * | ↔ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | |
Maximal respiration | ↔ | ↔ | ↔ | ↓ | ↓ | ↔ | ↔ | ↓ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | |
Spare respiratory capacity | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↔ | ↓ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | |
ATP- linked OCR | ↑ | ↑ | ↔ | ↓ | ↓ | ↓ | ↔ | ↓ | ↔ | ↓ | ↓ | ↓ | ↓ | ↓ | |
Non mito. respiration | ↑ | ↑ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
ATP | Levels | ↔ | ↔ | ↔ | ↓ | ↑ | ↔ | ↔ | ↓ | ↔ | ↔ | ↑ | ↔ | ↑ | ↑ |
autophagy markers | LC3-II | ↑ | ↑ | ↔ | ↔ | ↔ | ↔ | ↑ | ↓ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
p62 | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Complex I | Activity | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↓ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
Protein levels | ↑ | ↔ | ↔ | ↓ | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
Mito. Complexes II-V | CoII protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
CoIII protein levels | ↔ | ↔ | ↔ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | |
CoIV protein levels | ↑ | ↔ | ↔ | ↔ | ↔ | ↔ | ↑ | ↑ | ↔ | ↑ | ↔ | ↔ | ↔ | ↔ | |
CoV protein levels | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ | ↔ |
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Damri, O.; Natur, S.; Agam, G. Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells? Int. J. Mol. Sci. 2021, 22, 5753. https://doi.org/10.3390/ijms22115753
Damri O, Natur S, Agam G. Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells? International Journal of Molecular Sciences. 2021; 22(11):5753. https://doi.org/10.3390/ijms22115753
Chicago/Turabian StyleDamri, Odeya, Sarya Natur, and Galila Agam. 2021. "Do Autophagy Enhancers/ROS Scavengers Alleviate Consequences of Mild Mitochondrial Dysfunction Induced in Neuronal-Derived Cells?" International Journal of Molecular Sciences 22, no. 11: 5753. https://doi.org/10.3390/ijms22115753