The purpose of the Mammalian Mitochondrial Ribosomal Consortium is to:

1. Identify and characterize the structural components (proteins and genes) involved in mitochondrial translation and mitochondrial RNA processing;
2. Identify the possible role of these genes/proteins in human disease;
3. Devise diagnostic tests to identify these possible disease genes/proteins, and consider preventive and therapeutic approaches to these disorders.

    The ability of mitochondrial oxidative phosphorylation to meet the energy demands of cells is of paramount importance to cell survival and vitality, to normal developmental processes, tissue function, and disease prevention. Approximately 1000 nuclear encoded and 37 mitochondrial encoded genes are required for intrinsic mitochondrial function. Of the mitochondrial genes, 2 code for rRNAs and 22 code for tRNAs, components of the mitochondrial translation system responsible for translating the remaining 13 mitochondrial mRNAs, which code for subunits of the oxidative phosphorylation complexes. A collection of various mutations in mitochondrial rRNA and tRNA cause deafness, cardiomyopathy, myopathies, etc., and are associated with diabetes and obesity and thus vividly demonstrate the importance of efficient mitochondrial translation.

    Therefore it is our working hypothesis that mutations in the genes for mitochondrial ribosomal proteins (MRPs) will be responsible for human disease because they would also impair mitochondrial translation and oxidative phosphorylation. There are at least 84 MRPs that are encoded in the nucleus, translated on cytoplasmic ribosomes and imported into the mitochondrion. At this point we have cloned 32 genes and have shown that 13 do not have homologues in the ancestral bacterial ribosome and can not be recognized through database searches. We plan to clone and map the approximately 55 remaining human MRP genes. In so doing we will identify an additional 20 new genes (those without known function). Our determination of chromosomal map positions of the current 32 genes reveals that 17 MRP genes are candidates for growth retardation and hearing disorders. We are testing them on patient DNA to confirm our hypothesis. We expect that many of the remaining hMRPs genes will also be linked to clinically important genetic loci and thus by necessity be treated as candidate genes for these and other disorders.