Mitochondrial large ribosomal subunit (39S) (39S subunit)

The mitochondrial large ribosomal subunit (39S) is a complex ribonucleoprotein assembly essential for translating the 13 proteins encoded by mitochondrial DNA, all of which are core components of the oxidative phosphorylation system (Amunts et al., 2015, Science). It consists of the 16S ribosomal RNA and approximately 50 mitochondrial ribosomal proteins (MRPLs), which facilitate peptide bond formation at the peptidyl transferase center (Greber & Ban, 2016, Annual Review of Biochemistry). Due to its endosymbiotic bacterial ancestry, the 39S subunit is structurally similar to the bacterial 50S subunit, leading to off-target inhibition by antibiotics such as linezolid and chloramphenicol (Wilson, 2014, Nature Reviews Microbiology). This inhibition can result in clinical toxicities, including lactic acidosis and bone marrow suppression, due to decreased ATP production (Garrabou et al., 2010, Antimicrobial Agents and Chemotherapy). In oncology, the 39S subunit is being investigated as a target because many cancer cells rely on mitochondrial biogenesis for survival and metastasis (Skrtic et al., 2011, Cancer Cell). Furthermore, mutations in genes encoding 39S components are associated with severe metabolic disorders, such as Leigh syndrome and combined oxidative phosphorylation deficiency (Sylvester et al., 2004, Proteomics).

Other names

39S ribosomal subunitLarge mitochondrial ribosomal subunitmt-LSUMitochondrial 39S ribosomemTLSU

Inhibition of mitochondrial protein synthesis by binding to the peptidyl transferase center (PTC) or the exit tunnel of the 39S subunit, preventing the assembly of oxidative phosphorylation complexes (Wilson, 2014; Leach et al., 2007).