The Research Of Correlation Between PINK1-associated Protein And Mitochondrial Quality Control

Parkinson's disease(PD)is a degenerative disease in nervous system with degradation of nigra striatum dopamine neurons.Satic tremor,muscle stiffness,movement disorders,and balance disorders are its clinical symptoms.Mutation in PINK1 is the most frequent cause of PD.Lots of studies suggest that PINK1 is related to mitochondrial function,but the molecular mechanisms need further exploration.The mitochondrial quality control is important to maintain the stability of mitochondrial,such in morphology,motility,distribution,quantity.Mitophagy,fission and fusion can achieve multiple regulation of mitochondrial quality.This paper aims to further explore the relationship between quality control and PINK1 mutation in autosomal recessive hereditary PD and provides a new direction for further treatment of PD.Using a tandem affinity chromatography-mass spectrometry in Drosophlia and mammalian cell,we showed PINK1 and mitochondrial protein GGF located in a same complex and directly interact in physics and genetics.On this basis,we found PINK1 phosphorylate GGF protein and its phosphorylation site.We performed locus mutation to obtain GGF mutant transgenic flies and then crossed GGF mutant Drosophila with PINK1 strains.The number of dopamine neurons in F1 generations was detected using tissue immune staining at the particular area of brain,and the abnormal wings phenotype.Our results revealed the genetic interaction between PINK1 and GGF.At the cellular level,we used Cas9 technology to get GGF knock out monoclonal cells.However,only a hybrid cell line was obtained.According to the western blot results,the expression of GGF protein in heterozygous cells was reduced.Furthermore,our study found that the hybrid cell line did have a negative effect on the mitophagy.This study reveals that PINK1 and GGF regulate mitophagy and participate in mitochondrial quality control,a new pathway to maintain mitochondrial homeostasis.These findings may help us to further research of PD and provide a new clue of treatment.