Investigating the role of transcellular mitochondrial transfer in adult stem cells

About This Grant

Project Summary Tissue stem cells are the building blocks during development, and they play a critical role in tissue regeneration and homeostasis throughout life. However, aging results in a decline in proper regulation of stem cell activity, leading to loss of homeostasis over time. Previous work in the Jones Lab demonstrated an important role for mitochondrial biogenesis and turnover in the regulation of adult stem cell behavior in Drosophila melanogaster. However, the mechanisms by which these cells maintain healthy pools of mitochondria throughout life remain unknown. I recently found that male germline stem cells (GSCs) traffic mitochondria to adjacent, somatic niche cells. Since its discovery in 2006, intercellular mitochondrial transfer has been described as a means for stem cells to maintain homeostasis under a wide range of oxidative stressors; however, transfer in vivo under physiological conditions has not been demonstrated. GSCs possess microtubule-based nanotubes that protrude to adjacent somatic niche (hub) cells and are the correct size and shape to facilitate mitochondrial transfer. Preliminary data suggest that the transfer of mitochondria between GSCs and the soma is more pronounced under stressors such as age and a high fat diet. Germline-specific knock-down of genes known to regulate mitochondrial dynamics reduced the frequency of mitochondrial transfer. Therefore, I hypothesize that GSCs utilize intercellular mitochondrial transfer to maintain a healthy pool of mitochondria throughout the life. I will use Drosophila genetics and advanced imaging techniques to test this hypothesis and characterize the specific mechanisms regulating mitochondrial transfer. Upon completion, this project will provide a better understanding of how stem cells maintain high quality organelles throughout life. In addition, my work will have strong implications for organelle-based therapies for treating age-onset diseases.