PTEN-induced putative kinase 1 (PINK1) mutation induces autosomal recessive Parkinson's Disease (PD), mitochondrial dysfunction is the central pathogenic process. However, more and more studies presented the bulk of the damage to neurons with mitochondrial dysfunction stems from the endoplasmic reticulum (ER) stress. In mitochondria damaged PINK1B9 fly model how protein kinase RNA-like ER kinase (PERK) arm of ER stress functions remains a mystery. Thus, we generated both PERK overexpressed (PEK OE) and down expressed (PEK RNAi) PINK1B9 flies and monitored their motor activity. We found PEK OE decreased the abnormal wing posture rate and rescued PINK1B9 flies' motor activity. Furthermore, we observed the increased number of dopaminergic neurons of protocerebral posterior lateral 1 (PPL1) and the tyrosine hydroxylase (TH) protein levels in PINK1B9 flies. When testing the mitochondrial morphology in flight muscle with TEM, we found that the shape of the mitochondria became normal. The ATP levels of flight muscle tissues were significantly elevated in PEK OE PINK1B9 flies with the increased function of mitochondrial Electron Transport Chain (ETC) Complex I (CI) but not Complex Ⅱ (CⅡ) which is further confirmed by oxygen consumption experiments, Western Blot, and RT-PCR to examine the corresponding subunits. We suggest that overexpression of PERK can rescue PINK1B9 PD flies' pathogenic phenotypes and it is linked with the improved mitochondrial function especially CI of ETC but not CⅡ. Our findings may pave a way for the target of the drug for alleviating the suffering of PINK1 mutant autosomal recessive PD patients.
