The role of protein kinase RNA-like ER kinase (PERK) arm of the unfolded protein response (UPR) in PTEN-induced putative kinase 1 (PINK1) mutant Parkinson’s Disease (PD) flies is not well studied and its exact role in mitochondrial function is unknown.

Mutation in PINK1 causes autosomal recessive PD, mitochondrial dysfunction is thought to be the central pathogenic process. However, the damage to neurons with mitochondrial dysfunction stems from the endoplasmic reticulum (ER) stress is demonstrated recently. How PERK arm of UPR functions in PINK1^B9 fly model remains a mystery.

We generated MHC-Gal4 driven PERK over expressed and down expressed PINK1^B9 flies and conducted specific testing.

We found that over-expression of PERK decreased the abnormal wing posture rate and rescued PINK1^B9 flies motor activity which further induced eIF2α phosphorylation level. We then examined the number of DA neurons with anti-TH staining cell bodies of PPL1 in PINK1^B9 flies, surprisingly we found that in PERK over expressed group the number of cell bodies increased significantly. We then tested mitochondrial morphology via TEM and found that the shape of the mitochondria became normal. We measured ATP levels of muscle tissues and found that in PERK up-regulated PINK1^B9group ATP levels elevated significantly. By conducting Western Blot, we tested the most important marker NDUFS3 for Complex I and found its expression was increased in rescued group.When examined by O2K for mitochondrial function we found that PERK over-expression in PINK1^B9 flies mainly improved Complex I function not Complex ?.