The Study Of CG12091 On Neuronal Homeostasis Maintenance In Drosophila

Mitochondrial dysfunction,and abnormal energy metabolism,has become a recognized early pathological phenomenon in neurodegenerative diseases.Post-translational modifications(PTMs)of mitochondrial proteins can strictly regulate the structure,localization and interaction of mitochondrial proteins and therefore are important for mitochondrial functions.In this study,we identified that deletion of CG12091,a potential mitochondrial PP2 C phosphatase gene,resulted in changes in mitochondrial morphology and neurodegeneration in Drosophila.The over-expression of CG12091 severely affected the development of Drosophila compound eye.The adult fly eyes with CG12091 overexpressed became smaller and rougher.The electron microscopy assays indicated fusion between the ommatidium,increased the number of rhabdomere per ommatidium,and damaged mitochondria in the photoreceptor cells.RNAi knockdown of CG11267 and CG5261 partly phenocopy the overexpression of CG12091.CG11267 and CG5261 are homologous genes of HSP10 and lat1 in Drosophila,respectively.HSP10 is a component of HSP60/HSP10 complex,which can help proteins enter mitochondria and fold correctly.Lat1 participates in TCA cycle and is a subunit of pyruvate dehydrogenase complex.Surprisingly,overexpression of phosphatase-inactivated form of CG12091 also led to defects in Drosophila compound eye,similar but less severe than that in the fly eyes with wild-type CG12091 overexpression.It suggested that CG12091 may have phosphatase independent functions in Drosophila.PPTC7,the homologous protein of Drosophila CG12091,is located in both the outer mitochondrial membrane and matrix in cultured mammalian cells.Its deletion leads to the mis-localization of the mitochondrial matrix protein HSP60 to cytoplasm and a decrease of ATP synthesize and spare respiratory capacity in mitochondria.The cells lack of PPTC7 are more vulnerable to oxidative stress than the control cells.In conclusion,this study found that CG12091 hand its human homologous protein PPTC7 are important for the mitochondrial function and neuronal homeostasis.