Mammalian mitochondrial ribosome (mitoribosome) (mitoribosome)

The mammalian mitochondrial ribosome, or mitoribosome, is a specialized ribonucleoprotein complex located within the mitochondrial matrix that is essential for the synthesis of 13 proteins encoded by mitochondrial DNA (mtDNA) [Greber & Ban, 2016]. These 13 proteins are critical subunits of the oxidative phosphorylation (OXPHOS) system, which generates the majority of cellular ATP [Amunts et al., 2015]. Structurally, the mammalian mitoribosome is a 55S particle composed of a small 28S subunit and a large 39S subunit, featuring a significantly higher protein-to-RNA ratio than bacterial or cytosolic ribosomes [Greber & Ban, 2016]. Due to its evolutionary descent from alphaproteobacteria, the mitoribosome shares structural conservation with bacterial ribosomes, leading to off-target inhibition by several classes of antibiotics such as tetracyclines and aminoglycosides [Wilson, 2014]. This cross-reactivity can result in clinical toxicities like ototoxicity, myelosuppression, or lactic acidosis [Wilson, 2014]. However, this same sensitivity is being explored as a therapeutic vulnerability in oncology, particularly in cancers like acute myeloid leukemia that exhibit a high dependency on mitochondrial biogenesis and OXPHOS [Skrtic et al., 2011]. Mutations in mitoribosomal proteins or rRNA are also linked to various mitochondrial diseases, including Leigh syndrome and non-syndromic deafness [Gorman et al., 2016].

Other names

55S ribosomeMitochondrial ribosomemRNPMitoribosome

Inhibition of mitochondrial protein translation by binding to the 28S or 39S subunits, thereby disrupting the synthesis of essential OXPHOS components [Wilson, 2014; Skrtic et al., 2011].