Mol Biol Cell

NOA1 is an evolutionarily conserved GTP binding protein, which localizes predominantly to mitochondria in mammalian cells. Based on bioinformatic analysis we predicted its possible involvement in ribosomal biogenesis, although, this had not been supported by any experimental evidence. Here we determine NOA1 function through generation of knock-out mice and in-vitro assays. NOA1 deficient mice exhibit mid-gestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from NOA1 knock-out embryos show deficient mitochondrial protein synthesis and a global defect of oxidative phosphorylation (OXPHOS). Additionally, Noa1-/- cells are impaired in staurosporine induced apoptosis. The analysis of mitochondrial ribosomal subunits from Noa1-/- cells by sucrose gradient centrifugation and Western blotting showed anomalous sedimentation, consistent with a defect in mitochondrial ribosome assembly. Further, in vitro experiments revealed that intrinsic NOA1 GTPase activity was stimulated by bacterial ribosomal constituents. Taken together, our data show that NOA1 is required for mitochondrial protein synthesis, likely due to its yet unidentified role in mitoribosomal biogenesis. Thus, NOA1 is required for such basal mitochondrial functions as ATP synthesis and apoptosis