Mammalian and mitochondrial ribosomes (80S and 55S ribosomes)

Mammalian and mitochondrial ribosomes are the complex ribonucleoprotein machineries responsible for protein synthesis within eukaryotic cells. The mammalian cytosolic ribosome (80S) translates the vast majority of the proteome, while the mitochondrial ribosome (mitoribosome, 55S) is specialized for synthesizing 13 essential components of the oxidative phosphorylation system (Amunts et al., 2015, Science; Greber & Ban, 2016, Annu Rev Biochem). While bacterial ribosomes are the primary targets for many antibiotics, the structural similarity between bacterial and mitochondrial ribosomes often leads to off-target inhibition of the latter, resulting in clinical toxicities such as myelosuppression, lactic acidosis, and ototoxicity (Garrabou et al., 2010, Antimicrob Agents Chemother). In oncology, these ribosomes are increasingly viewed as therapeutic targets because cancer cells exhibit a high demand for protein synthesis and ribosome biogenesis to support rapid proliferation (Pelletier et al., 2015, Nat Rev Drug Discov). Drugs targeting these complexes typically act by binding to specific ribosomal subunits (e.g., 40S, 60S, 28S, or 39S) to arrest translation elongation or initiation, thereby inducing cell cycle arrest or apoptosis (Wilson, 2014, Nat Rev Microbiol).

Other names

80S ribosome55S ribosomeMitoribosomeCytosolic ribosomeEukaryotic ribosome

Inhibition of protein synthesis by binding to ribosomal subunits (40S, 60S, 28S, or 39S), blocking peptide bond formation, or interfering with translocation.