Eukaryotic ribosome (cytosolic and mitochondrial) (80S and 55S Ribosomes)

The eukaryotic ribosome is the fundamental macromolecular machine responsible for translating genetic information into proteins. In human cells, this machinery exists in two distinct forms: the cytosolic 80S ribosome and the mitochondrial 55S ribosome (mitoribosome) [PMID: 25635023]. The cytosolic ribosome synthesizes the vast majority of cellular proteins, while the mitoribosome is specialized for the synthesis of 13 essential subunits of the mitochondrial electron transport chain [PMID: 29415870]. These structures are critical therapeutic targets; for instance, omacetaxine mepesuccinate is an FDA-approved drug that inhibits the cytosolic ribosome to treat chronic myeloid leukemia [PMID: 23532266]. However, the structural similarity between the mitoribosome and bacterial ribosomes often leads to off-target inhibition by antibiotics like aminoglycosides and linezolid, resulting in clinical toxicities such as ototoxicity and myelosuppression [PMID: 25635023]. Furthermore, mutations in ribosomal proteins or assembly factors lead to a group of disorders known as ribosomopathies, and the upregulation of ribosome biogenesis is a hallmark of many aggressive cancers [PMID: 30639241]. Consequently, the ribosome is increasingly viewed as a viable target for selective small-molecule inhibitors in oncology and other therapeutic areas.

Other names

Cytosolic ribosomeMitoribosome80S ribosome55S ribosomeMitochondrial ribosomeRibonucleoprotein complex

Inhibition of protein synthesis by blocking the peptidyl transferase center, interfering with tRNA binding at the A-site, or inducing translational misreading of mRNA.