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.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Macromolecular Structure and Function C Study Section (MSFC)
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Anderson, Vernon
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Pennsylvania State University
Schools of Arts and Sciences
University Park
United States
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Han, Min-Joon; Koc, Emine Cavdar; Koc, Hasan (2014) Post-translational modification and mitochondrial relocalization of histone H3 during apoptosis induced by staurosporine. Biochem Biophys Res Commun 450:802-7
Haque, Md Emdadul; Koc, Hasan; Cimen, Huseyin et al. (2011) Contacts between mammalian mitochondrial translational initiation factor 3 and ribosomal proteins in the small subunit. Biochim Biophys Acta 1814:1779-84
Han, Min-Joon; Cimen, Huseyin; Miller-Lee, Jennifer L et al. (2011) Purification of human mitochondrial ribosomal L7/L12 stalk proteins and reconstitution of functional hybrid ribosomes in Escherichia coli. Protein Expr Purif 78:48-54
Haque, Md Emdadul; Elmore, Kevin B; Tripathy, Ashutosh et al. (2010) Properties of the C-terminal tail of human mitochondrial inner membrane protein Oxa1L and its interactions with mammalian mitochondrial ribosomes. J Biol Chem 285:28353-62
Han, Min-Joon; Chiu, Daniel T; Koc, Emine C (2010) Regulation of mitochondrial ribosomal protein S29 (MRPS29) expression by a 5'-upstream open reading frame. Mitochondrion 10:274-83
Yang, Yongjie; Cimen, Huseyin; Han, Min-Joon et al. (2010) NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. J Biol Chem 285:7417-29
Cimen, Huseyin; Han, Min-Joon; Yang, Yongjie et al. (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49:304-11
Soung, George Y; Miller, Jennifer L; Koc, Hasan et al. (2009) Comprehensive analysis of phosphorylated proteins of Escherichia coli ribosomes. J Proteome Res 8:3390-402
Miller, Jennifer L; Cimen, Huseyin; Koc, Hasan et al. (2009) Phosphorylated proteins of the mammalian mitochondrial ribosome: implications in protein synthesis. J Proteome Res 8:4789-98
Miller, Jennifer L; Koc, Hasan; Koc, Emine C (2008) Identification of phosphorylation sites in mammalian mitochondrial ribosomal protein DAP3. Protein Sci 17:251-60