Control of Programmed Cell Death by GCN-1

Abstract

Apoptosis is a cell death phenomenon that is fundamental to the development of an organism and to the pathogenesis of disease states. Regulation of apoptosis occurs at various molecular steps, but its regulation at the translational level remains poorly understood. The phenomenon of germline apoptosis, either physiological (i.e., without stress) or stress-induced, occurs throughout eukaryotic organisms from worms to humans and may have a role in maintaining germline immortality by eliminating compromised germ cells. Therefore the ability to regulate germline apoptosis is intricately linked with the survival and fitness of species. GCN1, a known translational regulator, has been traditionally associated with GCN-2 to activate the Integrated Stress Response in order to modulate protein synthesis in the context of stress.

In the present study/thesis, we have discovered potentially a novel translational control mechanism of programmed cell death by GCN-1, pending further molecular studies. Contrary to conventional wisdom, this control occurs in a GCN-2 and Integrated Stress Response pathwayindependent manner, providing a non-canonical function to GCN-1. The present study also potentially provides further mechanistic understanding of the poorly understood biological phenomenon of germline programmed cell death; a biological process that initiates death to nurture life. The knowledge presented herein could help further understand human female reproductive physiology in order to potentially extend reproductive lifespan and mitigate oocyte loss and sterility caused by environmental stressors, such as radiation and chemotherapy.