Mitochondria have been shown to play a role in many human diseases. Specific mutations in the mitochondrial genome MARCH 9, 2001 MCCULLOCH, APRIL V. lead to a variety of multi-systemic disorders that affect the heart, nervous system and skeletal muscle. Mitochondrial dysfunction has also been implicated in Alzheimer?s disease, Parkinson?s disease, and in the control of apoptosis. Therefore, fully characterizing the requirements for proper mitochondrial gene expression in humans is critical, especially if one wants to understand how these processes can lead to specific disease states. The overall goal of this proposal is to characterize the proteins required for transcription initiation and transcription-coupled processes in human mitochondria, and there are three specific aims of the research project directed toward this goal.
The first aim i s to determine precisely which proteins make up the transcription complex in human mitochondria, as only two factors, h-mtTFA and h-mtRNA polymerase, are known to be required for mtDNA transcription. It has been found in the yeast Saccharomyces cerevisiae that an amino-terminal domain of mtRNA polymerase is required for maintenance of mtDNA and to couple R.NA processing events to transcription.
The second aim i s to determine if the amino-terminal extension of the human mtRNA polymerase forms a functional domain that couples other events to transcription. Finally, the candidate and the sponsor?s preliminary data suggest that h-mtRNA polymerase interacts with the mitochondrial ribosomal protein, MRPLI2. Because MRPL12 is encoded in the nucleus, this might be one means by which the nucleus could regulate gene expression in the mitochondria.
Specific aim three is to determine if this interaction is functionally significant and which processes are affected by this interaction in mitochondria.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL068459-03
Application #
6644888
Study Section
Special Emphasis Panel (ZRG1-BIO (20))
Program Officer
Commarato, Michael
Project Start
2002-09-27
Project End
2004-09-26
Budget Start
2003-09-27
Budget End
2004-09-26
Support Year
3
Fiscal Year
2003
Total Cost
$48,148
Indirect Cost
Name
Emory University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322