Protective role of Bre1 in mitochondrial function and energy metabolism in Drosophila models of Parkinson's disease

We discovered that Bre1 overexpression significantly improved the phenotype of PD flies and protected their dopaminergic neurons from degeneration. More significantly, we observed that the overexpression of Bre1 markedly enhanced the respiratory capacity of mitochondrial Complex I and Complex II, elevated ATP levels, reduced ROS levels, and improved mitochondrial structural integrity. The Western Blot results demonstrate a significant increase in the critical glycolysis enzymes, Pfk and Pyk proteins. Moreover, qRT-PCR results showed a remarkably upregulation in the transcriptional level of OGDH, a critical rate-limiting enzyme in the TCA cycle. Therefore, our study suggests that Bre1 improves the phenotypes of PD model flies by attenuating mitochondrial damage and enhancing energy metabolism, offering a potential drug target for ameliorating the symptoms of PINK1 mutant autosomal recessive PD patients.