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The **large mitochondrial ribosomal subunit** (mt-LSU) is the 39S component of the mammalian mitochondrial ribosome (mitoribosome), an essential machine for synthesizing 13 mitochondrial-encoded proteins critical for oxidative phosphorylation[5][1]. This ribonucleoprotein complex is highly divergent from bacterial and cytoplasmic ribosomes, featuring a drastically reduced rRNA core and an expanded set of proteins, many unique to mitochondria[2][1][7]. The mt-LSU includes the peptidyl transferase center, the nascent polypeptide exit tunnel, and a specialized central protuberance incorporating mitochondrial tRNA^Val^ as a structural component instead of the typical 5S rRNA[1][5][7]. It initiates and catalyzes peptide bond formation during translation of mtDNA-encoded membrane proteins, integrating them into the inner mitochondrial membrane to support electron transport and ATP generation[3][5]. Mutations in mt-LSU components are linked to a variety of human mitochondrial disorders, and many antibiotics can inadvertently inhibit this subunit, resulting in therapeutic challenges and side effects[1][4][9].
Inhibition of mitochondrial translation through binding to mitochondrial ribosomal subunits, interfering with the peptidyl transferase center or tRNA sites
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