The Role Of The Mitochondrial Fission Gene Drp-1 In Regulating Longevity In C.Elegans

Mounting evidence indicated that mitochondria can function as a signaling center in regulating life span. Known mitochondria pathways that affect longevity includes ROS, ETC, and mitochondria unfolded protein response. Mitochondria are dynamic organelle that undergo constant fission and fusion, the physiological significance of which is not well understood. A general view is that the mitochondria dynamics is connected to its protein homeostasis, energy balance, and quality control, all of which affects life span. However, the role of mitochondria dynamics genes in regulating life span has not been thoroughly examined.I take advantage of C. elegans as a genetic model to study the possible roles of mitochondria dynamics gene in life span regulation. A series of fluorescent protein marker were constructed to label mitochondria in live animals. The mitochondria morphology during the course of animal ageing were examined and imaged. I found the mitochondria become more fragmented in aged animals than young adults, in which the mitochondria tend to form network. The life span assays were carried out for mitochondria dynamics gene mutants. Both mitochondria fission gene and fusion gene mutants show the increase in life span, which suggested the perturbation of mitochondria dynamics either way can cause animals live longer.The interactions between drp-1 and other longevity pathways are tested. The results show that drp-1 mutation can cause additive effects on the increased life span for insulin-like signal (daf-2), protein homeostasis (TOR), and unfolded protein response (atfs-1). In contrast, drp-1 fail to further increase the life span increase in mitochondria ETC mutants, suggesting drp-1 function in the common pathway as ETC mutants. The double mutant of drp-1 and eat-2, which mimic the energy restriction, did not show further increase in longevity, suggesting drp-l’s role in life span regulation linked to energy balance.As the essential downstream of insulin-like signaling, the forkhead transcription factor daf-16 mutation can completely suppress the longevity of the drp-1 and daf-2 double mutants; whereas another transcription factor skn-1 failed to suppress the life span increase of drp-1 and daf-2. AMP-activated protein kinase aak-2 can not only suppress the life span of drp-1 and daf-2 double, and also suppress the drp-1 single mutant, suggesting aak-2 functions in the downstream pathways of drp-1 in life span regulation.The results together revealed the mitochondria dynamics is linked to life span regulation. The imbalance of ETC function and energy likely cause perturbations in mitochondria dynamics, consequently affecting longevity.