Nuclear MRP genes and mitochondrial disease.

The ancestral mitochondrial ribosome (70S) underwent major structural remodeling during the evolution of mammalian mitochondrial ribosomes (55S). Despite the loss of nearly half their RNA, 55S ribosomes are actually larger than bacterial ribosomes because of all the extra proteins they contain. Typical of mammalian mitochondrial ribosomes, the human mitochondrial ribosome is one of the most protein-rich ribosomes, containing several new proteins. One of the new proteins is a novel GTP binding protein, DAP3, that has been implicated in apoptosis. Except for DAP3, the locations of the individual new proteins in the ribosome are unknown. All of the MRPs are encoded by nuclear genes. Mutations or deficiencies of ribosome assembly proteins or other essential proteins are candidates for mitochondrial disease, since the mitochondrial ribosome translates mRNAs for the 13 essential components of the oxidative phosphorylation system. Several of the MRP genes map to loci associated with disorders consistent with impaired oxidative phosphorylation, such as Leigh Syndrome, multiple mitochondrial dysfunctions, and non-syndromic hearing loss. This manuscript reviews the distinctive properties of human mitochondrial ribosomes and ribosomal proteins, and the correlation of MRP3 gene locations with loci associated with disorders of energy metabolism, and provides localization information for one of the unusual proteins contained in human mitochondrial ribosomes, MRPS29.