Identification of genetic mechanisms preventing male mitochondrial inheritance

California State University Fresno, Fresno CA

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Abstract

? DESCRIPTION (provided by applicant): Sperm-borne (male) mitochondria that enter an oocyte are normally eliminated from most animal embryos immediately after fertilization. Although much is known about mechanisms that target unhealthy mitochondria for destruction using the autophagy pathway, it is unclear what cellular male surveillance mechanism accomplishes the task of specifically identifying sperm-transmitted mitochondria. Male mitochondrial transmission is most often observed in both inter-species and intra-species hybrids. This correlation suggests two possibilities. First, a heritable mechanism is responsible for male surveillance. Second, male mitochondrial transmission results from a hybrid genetic incompatibility that compromises this male surveillance system. The long-term objective of this research program is to elucidate the genetic mechanism regulating male mitochondrial transmission. Such a system must involve an embryonic mechanism to detect male mitochondria. This proposal tests the hypothesis that identification of male mitochondria is accomplished by a genetically-encoded male surveillance system. The approaches employ a powerful genetic model system, in which transmission of male mitochondria can easily be assessed, and complementary approaches to identify loci that are involved in male surveillance. The results of this study will improve our understanding of male surveillance mechanisms and inform future efforts to identify the genes involved. This knowledge will ultimately impact human health by enhancing our ability to identify and diagnose mitochondrial genetic disorders. Additionally, results from this research might suggest treatments that enable male mitochondrial transmission in situations where purely maternal inheritance would lead to transmission of a mitochondrial genetic disorder, such as Leber's Hereditary Optic Neuropathy (LHON).