Mitochondrial ribosome (mitoribosome) (mitoribosome)

The mitochondrial ribosome, or mitoribosome, is a specialized ribonucleoprotein complex located within the mitochondrial matrix responsible for translating the 13 essential protein subunits of the oxidative phosphorylation (OXPHOS) system encoded by mitochondrial DNA (mtDNA) (Greber & Ban, 2016). In humans, the 55S mitoribosome is composed of a small 28S subunit and a large 39S subunit, which are distinct from their cytosolic and bacterial counterparts in terms of protein-to-RNA ratio and structure (Amunts et al., 2015). Because of their evolutionary origin from alphaproteobacteria, mitoribosomes share structural similarities with bacterial ribosomes, making them unintended targets for several classes of antibiotics, such as aminoglycosides and oxazolidinones (Wilson, 2014). This off-target binding can lead to clinical toxicities, including ototoxicity and bone marrow suppression, by impairing mitochondrial energy production (Gootz et al., 1990). Conversely, mitoribosomes are emerging as therapeutic targets in oncology, as certain cancer cells exhibit a heightened dependency on mitochondrial translation for survival and metastasis (Skrtic et al., 2011). Mutations in mitoribosomal proteins or mitochondrial rRNA are also linked to a variety of inherited metabolic disorders, often presenting as encephalomyopathies or organ-specific failures (O'Brien, 2003).

Other names

Mitoribosome55S ribosomeMitochondrial protein synthesis machinery

Inhibition of mitochondrial protein synthesis by binding to the 28S or 39S subunits, thereby disrupting the translation of mtDNA-encoded subunits of the respiratory chain (Wilson, 2014).