Human mitochondrial ribosomes can switch their structural RNA composition

Significance Mammalian mitoribosomes are idiosyncratic. They reversed the typical 70% RNA:30% protein ratio to generate a protein-rich ribosome, which lacks the conventional 5S transcript as a third rRNA component. Recent subnanometer-resolution structures revealed a further unexpected eccentricity: integration of a mitochondrially encoded tRNA into the large-subunit structure. However, mitochondrially encoded tRNA (mt-tRNA) selection varies with mt-tRNA Val integration into human mitoribosomes compared with porcine mitoribosomes favoring mt-tRNA Phe . Our analysis of mitoribosomes from multiple tissues isolated from different mammals found that of 22 mitochondrially encoded tRNAs, only mt-tRNA Val or mt-tRNA Phe is incorporated. Further, there was no evidence of tissue-specific selectivity. Remarkably, human mitoribosomes can exhibit adaptive plasticity when mt-tRNA Val levels are severely depleted by selectively integrating mt-tRNA Phe instead, to generate translationally competent mitoribosomes.