Summary of R35 GM118188 (Xue, PI) Project title Fundamental mechanisms of paternal mitochondrial elimination and radiation-induced bystander effects Project summary Paternal mitochondrial elimination and radiation-induced bystander effects are two vitally important, distinct, and dynamic biological processes essential for animal development, stress response, and organismal fitness. Defects in these two important processes can cause various pathological conditions and disease. In this proposed work, we will carry out molecular genetic, reverse genetic, biochemical, cell biological and proteomic analyses to decipher basic mechanisms that regulate paternal mitochondrial elimination and radiation-induced bystander effects. For the study of paternal mitochondrial elimination, we hope to understand how paternal mitochondria are selectively impaired, recognized and removed in fertilized eggs, what paternal and maternal mechanisms are employed to specifically eliminate paternal mitochondria, and why paternal mitochondria need to be removed to ensure animal development and cell and organismal fitness. For the study of radiation- induced bystander effects, we plan to identify factors involved in triggering bystander effects in unexposed cells, signal pathways that mediate different bystander responses, and the mechanistic basis of bystander responses to other stresses. These studies should reveal novel mechanisms, pathways, and genes that control these two fundamental biological processes, and ultimately, provide new targets, ideas, and strategies to facilitate treatment of numerous human diseases caused by abnormalities in paternal mitochondrial elimination and improve disease treatment by reducing side effects caused by radiotherapy and other therapeutic treatments.

Contact PD/PI: XUE, DING Project Narrative Paternal mitochondrial elimination and radiation-induced bystander effects are two vitally important, distinct, and dynamic biological processes essential for stress response, normal cell functions and organismal development. Defects in these two processes can cause multiple human diseases, such as inherited human mitochondrial diseases. This proposal seeks to understand the mechanisms that regulate and execute these two fundamental biological events and identify new genes and pathways important for these two processes, leading to identification of new therapeutic targets or ideas to treat human diseases caused by abnormalities in paternal mitochondrial elimination and improve disease treatment by reducing side effects caused by radiotherapy and other therapeutic treatments. Project Narrative Page 7