The effect of mutated mitochondrial ribosomal proteins S16 and S22 on the assembly of the small and large ribosomal subunits in human mitochondria

Abstract

Mutations in mitochondrial small subunit ribosomal proteins MRPS16 or MRPS22 cause severe, fatal respiratory chain dysfunction due to impaired translation of mitochondrial mRNAs. The loss of either MRPS16 or MRPS22 was accompanied by the loss of most of another small subunit protein MRPS11. However, MRPS2 was reduced only about 2-fold in patient fibroblasts. This observation suggests that the small ribosomal subunit is only partially able to assemble in these patients. Two large subunit ribosomal proteins, MRPL13 and MRPL15, were present in substantial amounts suggesting that the large ribosomal subunit is still present despite a nonfunctional small subunit.

Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome

“…These data suggest that MRPS34 plays an important role in stabilizing the 12S rRNA and is required for the stability of the small mitoribosomal subunit. The relative sparing of the large mitoribosomal subunit in MRPS34-deficient cells is consistent with studies examining cell lines from subjects with pathogenic mutations in other small mitoribosomal subunit proteins MRPS16 and MRPS22, 57 suggesting that the maintenance of large and small mitoribosomal subunit levels are not inextricably linked in humans. While the identification of affected subjects with pathogenic mutations in mitoribosomal subunit proteins enables key insight into mitoribosome stability, more comprehensive studies are required to enable an intimate understanding of mitochondrial ribosomes and protein synthesis.…”

Mutation in mitochondrial ribosomal protein MRPS22 leads to Cornelia de Lange-like phenotype, brain abnormalities and hypertrophic cardiomyopathy

“…Recently, a MRPS22 defect was shown to strongly hamper assembly of the small ribosomal subunit, whereas assembly of the large subunit and part of the small subunit were only mildly affected. 30 This is consistent with both our and previous findings that mutations in mitochondrial ribosomal small subunit proteins cause a marked decrease in the abundance of the 12S rRNA transcript and nearly no reduction in the level of 16S rRNA, 6,7 as rRNAs are readily degraded unless they are incorporated into a ribosomal subunit. 31 Thus, although MRPS22 is evolutionary not well conserved, it is indispensable for the assembly of the human mitochondrial ribosome and consequently, as we have shown, for effective mitochondrial protein synthesis.…”

“…31 Thus, although MRPS22 is evolutionary not well conserved, it is indispensable for the assembly of the human mitochondrial ribosome and consequently, as we have shown, for effective mitochondrial protein synthesis. Previously, a missense mutation in MRPS22 (Arg170His) 7 and a non-sense mutation in MRPS16 (Arg111X), 6 which is highly conserved and essential for ribosome assembly, 29,30,32 were reported to be lethal. The clinical phenotypes of patients with MRPS16 or MRPS22 mutations bear resemblances.…”

Properties of the C-terminal Tail of Human Mitochondrial Inner Membrane Protein Oxa1L and Its Interactions with Mammalian Mitochondrial Ribosomes

“…Samples were run on a 15% SDS-PAGE. Proteins were transferred to PVDF membranes (Millipore) and probed with Oxa1L-CTT polyclonal antibody using the ECL Western blotting method as described (22).…”