Human mitochondrial ribosome (mitoribosome) (mitoribosome)

The human mitochondrial ribosome (mitoribosome) is a specialized 55S ribonucleoprotein complex responsible for translating the 13 essential protein subunits of the oxidative phosphorylation (OXPHOS) system encoded by mitochondrial DNA (mtDNA) [1, 2]. Located within the mitochondrial matrix, it consists of a small 28S subunit and a large 39S subunit, which are structurally distinct from the cytosolic 80S ribosome but share evolutionary ancestry with bacterial 70S ribosomes [3, 4]. This structural similarity is the primary cause of off-target toxicity for several classes of antibiotics, such as oxazolidinones and aminoglycosides, which can inadvertently inhibit mitochondrial translation in human cells [5]. Beyond its role in antibiotic toxicity, the mitoribosome is a critical factor in mitochondrial diseases, where mutations in its components lead to impaired energy production and multi-system failure [6]. It is also increasingly recognized as a therapeutic target in oncology, as many cancer cells rely on mitoribosome-mediated biogenesis to maintain metabolic plasticity and survive under stress [7]. Therapeutic strategies targeting the mitoribosome aim to either mitigate the side effects of existing drugs or exploit its unique structure to treat mitochondrial-dependent malignancies [5, 6].

Other names

55S ribosomeMitochondrial ribosomemitoribosomeMitochondrial protein synthesis complex

Inhibition of mitochondrial protein synthesis by binding to the 39S large subunit or 28S small subunit, thereby disrupting the assembly of the oxidative phosphorylation system.