The Role Of Drp-1 And Mitochondrial Genes In Regulating The Longevity In C. Elesans

Objective We used the C.elegans to be a animal model in this experiment and screen genes which controled the mitochondrial dynamics by the forward genetics research method, then discuss the function of these genes in the C.elegans. Methods We used GFP marker to label mitochondrial in specific neurons and epidermis by transgenic technology respectively, then a model which can observe mitochondrial in vivo was eastablished. Next, we used EMS mutagenesis to screen some mutants on the basis of the morphology and distribution of mitochondral. Then we mapped mutants by SNP marker. In order to detect the gene function, we further analyzed the relationship between drp-1 or other mitonchondrial genes and lifespan in the C.elegans. Results Through genetic screening, we received two mutants associated with mitochondrial dynamics, among them, the ybq1 can result in mitochondrial hyperfusion, and ybq3 can inhibit ybq1 caused by mitochondrial hyperfusion phenomenon. We knowed ybq1 was drp-1 mutant, and ybq3 was mapped to the location of the chrⅡ-6~ chrⅡ+4.After that, we also found that mitochondrial matrix 、 nucleoid and mtDNA were abnomal distribution and number. Then, we further analyzed the function of drp-1 in C.elegans. Results showed that drp-1 mutant was more sensitive to high temperature,but drp-1 mutant had a certain resistance to UV irradiation. In terms of C.elegans laying, drp-1 mutant had led to a sharp drop in the number of offspring. In terms of life adjustment, drp-1 mutant had a longer life expectancy than wildtype, and 0.1 mM PQ can increase ybq1 lifespan. When we overexpressed the drp-1 in wildtype, the C.elegans also can increase the lifespan. In addition, we also tested the other mitochondrial dynamic related genes whether involved in C.elegans lifespan or not.Results showed that fis-1(tm1867)and eat-3(tm1107) also can increase the lifespan of the C.elegans, but the former can’t increase the lifespan by 0.1 mM paraquat again,while the latter can be. However, fzo-1(tm1133) was not able to increase the life of the C.elegans. Conclusion In conclusion, drp-1 can control mitochondrial fission and the distribution and number of mitochondrial components. Mitochondrial fusion may need the ybq3. The reasons that drp-1 impacted on lifespan was various,regardless of its inactivation, or overexpress, all incresed the lifespan of the C.elegans.In addition, the reasons that drp-1 impacted on the lifespan was not caused by ROS response, but it likely owed to the ability of reproduction and resistance to stress from enviorment. In the end, eat-3 and fis-1 also affected the lifespan, but the mechanism was different. fis-1 regulated the C.elegans lifespan by ROS response and independent of reproduction, however, eat-3 which regulated the lifespan do not participate in the ROS response.