Hsp22 Protects Against Mitochondrial Dysfunction In PINK1 Mutant Transgenic Drosophila

Objective: To investigate the effect of Shock Protein Heat 22(Hsp22)on a classical PD transgenic Drosophila model——PINK1B9(which is the null mutation of PINK1 gene), and clarify the effect of Hsp22 in improving mitochondrial function of PINK1B9, and to further explore whether the mechanism is associated with ND42, which is a subunit of mitochondrial respiratory chain Complex I. Methods: In this study,MHC-Gal4 specific promoter is used to induce PINK1B9 specifically expression in drosophila muscle to establish the GAL4/UAS system model of PD transgenic Drosophila model. Further, use MHC-Gal4 promoter to drive Hsp22 over-expressed in PINK1B9, and observe the abnormal wing postures, flight rates, indirect flight muscle and mitochondrial morphology. And then choose ATP Determination Kit to test the ATP production, Mitochondrial Complex I Activity Assay Kit to test the activity of complexⅠ(CI).The mRNA level of ND42 and protein expression of NDUFS3(another subunit of CI) are respectively detected by real time PCR and Western blot. In order to study the role of ND42 in Hsp22, use ND42 RNA interference to intervene the Hsp22 in PINK1B9 flies, and also observe the phenotypes, indirect flight muscular and mitochondrial morphology of the flies, finally detect the analogous mitochondrial function. Results: Compared with the control group, PD transgenic Drosophila show abnormal wings, poor flying ability, irregular arrangement of indirect flight muscle, fractured muscle fiber, vacuoles formation, swollen mitochondria, damaged mitochondrial structure,decreased mitochondrial ATP production and activity of complex Ⅰ.When Hsp22 is overexpressed in PINK1B9 transgenic Drosophila, the defects of phenotypes are rescued, the mitochondrial structure and function are remarkably recovered. ND42 can completely weaken the protective effect of Hsp22 in PINK1B9.Conclusions: Hsp22 can protect against mitochondrial dysfunction in PINK1 mutant transgenic drosophila;The down-regulation of ND42, reduced the protective effect of Hsp22 in PINK1 mutation flies, supposing that ND42 plays an important role in the protection.