This proposal is aimed at exploring the detailed molecular interactions between factors encoded in the nuclear genome with factors encoded by the mitochondrial genome. Dr. Moraes, who has extensive experience in characterizing mtDNA mutations in patients with various human mitochondropathies, here aims to study the interaction between factors encoded by the nuclear and mitochondrial genomes by creating and characterizing a heterologous system of primate cell lines harboring nuclear DNA from one species and mitochondrial DNA from another, so-called """"""""xenomitochondrial cybrids."""""""" Thus, biological functions that involve coordinated participation of nuclear-coded and mtDNA-coded factors may be affected in these cell lines. The P.I. suggests that biochemical and molecular studies of these cell lines will shed light on many nDNA-mtDNA interactions that are needed for mtDNA transcription and replication, assembly of respiratory complexes and ATP production, mitochondrial protein synthesis, mitochondrial posttranscriptional modifications of RNA, mtDNA heteroplasmy dynamics, and mtDNA recombinations, all of which are essential for the establishment and maintenance of an efficient ATP generating system.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM055766-02
Application #
2701833
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1997-05-01
Project End
2001-04-30
Budget Start
1998-05-01
Budget End
1999-04-30
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146