The mammalian mitochondrial translation system is a very unique system and is one of the least understood systems of all. Besides their primary roles in protein biosynthesis, mammalian mitochondrial ribosomes are involved in apoptosis and various mitochondrial disease states. Mitochondrial ribosomes resemble the bacterial ribosomes; however, approximately half of the mitochondrial ribosomal proteins do not have any homologs among the bacterial and cytoplasmic ribosomal proteins. The major focus of the proposed research is to determine the roles of newly identified proteins in protein synthesis machinery of the mitochondria. Some of the proteins with the bacterial homologs are responsible for mRNA, tRNA, and factor binding to ribosomes. A number of the crucial bacterial ribosomal proteins are missing in the mammalian mitochondrial ribosome. The new class ribosomal proteins replacing the missing bacterial homologs will be determined in the localization and ligand binding experiments using proteomics approaches. In addition, we have discovered the presence of three different variants of S18s (MRP-S18s) in the small subunit of mitochondrial ribosomes using a proteomics approach. This finding clearly implies the presence of three conformationally different sub-populations of small subunits in mitochondrial ribosomes. In this proposal, we are proposing to study roles and functions of the new class ribosomal proteins and the three different variants of MRP-S18s in the protein biosynthesis in mammalian mitochondria. Furthermore, studies on post-translational modifications of these proteins will enable us to better understand the regulation of the mitochondrial translational machinery in disease states and apoptosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM071034-03
Application #
7277315
Study Section
Macromolecular Structure and Function C Study Section (MSFC)
Program Officer
Ikeda, Richard A
Project Start
2005-08-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
3
Fiscal Year
2007
Total Cost
$264,310
Indirect Cost
Name
Pennsylvania State University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
003403953
City
University Park
State
PA
Country
United States
Zip Code
16802
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