As the primary location for cellular metabolism, mitochondria pla a critical role in the function and survival of organ systems and ultimately the organism. A key component of this process, the mitochondrial DNA (mtDNA), is self-replicating and necessary for normal survival. Studies over the past two decades have identified the major molecules responsible for replicating mtDNA, yet essentially nothing is known about how the process of mtDNA synthesis is regulated. The long range goal of this effort is to identify thos regulatory mechanisms whose disruption result in often severe disease phenotypes. The primary goal of this proposal is to develop a novel model system in which the key steps in the regulation of mtDNA replication can be identified, described and experimentally manipulated. Maternal patterns of mitochondrial inheritance create significant barriers to experimental studies of mtDNA replication. In bivalves there exists a novel type of mitochondria inheritance involving female(F) and male(M) forms of mtDNA that are inherited in a reproducible, sex-specific pattern. A key part of this process is the selective amplification of the male mtDNA. The initial phase of the project will define spatial and temporal characteristics of (M) mtDNA replication in this system. In phase two, the dual inheritance model will be used to identify the key elements that regulate (M) mtDNA replication, distinguishing the relative roles of the structure, and the mtDNA. With the key component(s) identified, it will be possible to quantitatively and qualitatively determine how specific components of the replication machinery interact to regulate the process of mtDNA replication in normal and disease states.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21GM057237-02
Application #
2900917
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1998-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2001-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of South Carolina at Columbia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208