Ribosome biogenesis and function in human mitochondria
Mitochondria, which fulfill many essential roles within the cell, still contain their own genome (mtDNA). However, the expression of mtDNA-encoded proteins depends on factors encoded by the nuclear genome. Defects in these factors lead to severe human mitochondrial diseases. This is also true for the mitochondrial ribosomal proteins, which need to be imported into mitochondria, where they assemble with mtDNA-encoded ribosomal RNAs.
We are interested in how the human mitochondrial ribosome assembles from components of dual genetic origin. Although the mitochondrial ribosome arose from a bacterial ancestor, there are substantial differences in their structure and composition. Therefore, it is reasonable to speculate that the assembly pathways of bacterial and human mitochondrial ribosomes vary as well. The maturation of the mitochondrial ribosome requires the assistance of auxiliary factors, including RNA helicases, RNA-modifying enzymes, chaperones and GTPases, to ensure the folding of the ribosomal RNAs and proteins into the functional ribosomal subunits. Our work reveals the function and hierarchical order of action of ribosome biogenesis factors which might broaden our understanding of the diverse clinical presentations of a growing group of patients exhibiting mitochondrial translation deficiency.