Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases
Abstract
:1. Introduction
2. Mitochondrial Fusion and Fission
3. Dynamin-Related Protein 1
4. Drp1 Structure
5. Drp1 Functions
Drp1 Knockout Studies
6. Drp1 and Abnormal Mitochondrial Dynamics
6.1. Drp1 and Alzheimer’s Disease
6.2. Drp1 and Huntington’s Disease
6.3. Drp1 and Amyotrophic Lateral Sclerosis
6.4. Drp1 and Parkinson’s Disease
6.5. Drp1 and Multiple Sclerosis
6.6. Drp1 and Down Syndrome
6.7. Drp1 and Diabetes/Obesity
7. Mechanism of Mitochondrial Dysfunction via Drp1 Phosphorylation
8. Mitochondrial Division Inhibitors and their Protective Effects
8.1. Mdivi 1
8.1.1. Genetic Studies
8.1.2. Pharmacological Studies
8.2. P110
8.3. Dynasore
8.4. DDQ
9. Is Mitochondrial Division Inhibitor 1 a Drp1 Inhibitor?
10. Conclusions and Future Directions
Author Contributions
Funding
Conflicts of Interest
References
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Cell Type | Regulator Enzyme | Phosphoryl Group Addition Site | Effect | Citation |
---|---|---|---|---|
Mouse cortical neurons | Cdk5-mediated Drp1 phosphorylation at Ser579 is required for Aβ1-42 induced mitochondrial fission—GTPase domain activity is increased | Cdk5 could phosphorylate the recombinant Drp1 at Ser579. Aβ42 stimulation increased the phosphorylation level of Drp1. Cdk5 inhibitor roscovitine and knockdown of Cdk5 efficiently prevented Aβ42 induced Drp1 phosphorylation in neurons | Drp1 phosphorylation is activated by Ser579 | Guo et al. (2018) [61] |
HeLa (cervical cancer cells derived from Henrietta Lacks) Cyclin-dependent kinase 1 (Cdk1) | Ser385 (splice variant 1 of rat Drp1 Ser616), does not affect GTPase domain activity | Drp1 is activated during cell division when it accepts phosphoryl group from Cdk1 | Drp1 is activated during cell division when it accepts phosphoryl group from Cdk1 | Taguchi et al. (2007) [62] |
HeLa | Protein kinase A (PKA) | Ser637 of Drp1’s GTPase effector domain | Drp1 GTPase domain activity is inhibited when phosphorylated by PKA | Chang and Blackstone (2007) [63] |
HeLa neurons | Ca2+ calmodulin dependent PKI 1 (CaMKIα) | Ser600 (the Drp1 splice variant of Ser637) | Phosphorylation by CaMKIα activates Drp1 | Han et al. (2008) [64] |
Neonatal cardiomyocytes | Pim-1 | Ser637 | Drp1 phosphorylation by Pim-1 stops fission | Din et al. (2013) [65] |
PC12 | PKA, Calcineurin, and calcium coupling | Ser656 (splice variant 1 of rat Drp1 Ser637), does not affect GTPase domain activity | Phosphoryl group is transferred from PKA to Drp1, which stops GTPase activity, and inhibits apoptosis Calcineurin and calcium work to dephosphorylate and activate Drp1, which upregulates apoptosis | Cribbs and Strack (2007) [66] |
Calcineurin and calcium coupling | Ser637 | Calcineurin and calcium work to dephosphorylate and activate Drp1, which upregulates apoptosis | Cereghetti et al. (2008) [67] |
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Oliver, D.; Reddy, P.H. Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases. Cells 2019, 8, 961. https://doi.org/10.3390/cells8090961
Oliver D, Reddy PH. Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases. Cells. 2019; 8(9):961. https://doi.org/10.3390/cells8090961
Chicago/Turabian StyleOliver, Darryll, and P. Hemachandra Reddy. 2019. "Dynamics of Dynamin-Related Protein 1 in Alzheimer’s Disease and Other Neurodegenerative Diseases" Cells 8, no. 9: 961. https://doi.org/10.3390/cells8090961