| First Author | Pathak D | Year | 2017 |
| Journal | eNeuro | Volume | 4 |
| Issue | 2 | PubMed ID | 28462393 |
| Mgi Jnum | J:255900 | Mgi Id | MGI:6114613 |
| Doi | 10.1523/ENEURO.0216-16.2017 | Citation | Pathak D, et al. (2017) Loss of alpha-Synuclein Does Not Affect Mitochondrial Bioenergetics in Rodent Neurons. eNeuro 4(2):ENEURO.0216-16.2017 |
| abstractText | Increased alpha-synuclein (alphasyn) and mitochondrial dysfunction play central roles in the pathogenesis of Parkinson's disease (PD), and lowering alphasyn is under intensive investigation as a therapeutic strategy for PD. Increased alphasyn levels disrupt mitochondria and impair respiration, while reduced alphasyn protects against mitochondrial toxins, suggesting that interactions between alphasyn and mitochondria influences the pathologic and physiologic functions of alphasyn. However, we do not know if alphasyn affects normal mitochondrial function or if lowering alphasyn levels impacts bioenergetic function, especially at the nerve terminal where alphasyn is enriched. To determine if alphasyn is required for normal mitochondrial function in neurons, we comprehensively evaluated how lowering alphasyn affects mitochondrial function. We found that alphasyn knockout (KO) does not affect the respiration of cultured hippocampal neurons or cortical and dopaminergic synaptosomes, and that neither loss of alphasyn nor all three (alpha, beta and gamma) syn isoforms decreased mitochondria-derived ATP levels at the synapse. Similarly, neither alphasyn KO nor knockdown altered the capacity of synaptic mitochondria to meet the energy requirements of synaptic vesicle cycling or influenced the localization of mitochondria to dopamine (DA) synapses in vivo. Finally, alphasyn KO did not affect overall energy metabolism in mice assessed with a Comprehensive Lab Animal Monitoring System. These studies suggest either that alphasyn has little or no significant physiological effect on mitochondrial bioenergetic function, or that any such functions are fully compensated for when lost. These results implicate that alphasyn levels can be reduced in neurons without impairing (or improving) mitochondrial bioenergetics or distribution. |
