Mitochondrial small ribosomal subunit (28S subunit) (28S subunit)

The mitochondrial small ribosomal subunit (28S) is a specialized ribonucleoprotein complex essential for the translation of the 13 polypeptides encoded by mitochondrial DNA (mtDNA), all of which are core components of the oxidative phosphorylation (OXPHOS) system (Source: UniProt, P0DPB3; Amunts et al., 2015, Science). Structurally distinct from its cytosolic counterpart, the 28S subunit consists of the 12S ribosomal RNA and approximately 30 mitoribosome-specific proteins (Source: NCBI, Gene ID: 64963). In clinical oncology, the 28S subunit has emerged as a target because many cancer cells, particularly leukemic stem cells, exhibit a high dependency on mitochondrial biogenesis and OXPHOS for survival (Source: Skrtic et al., 2011, Cancer Cell). Antibiotics such as tigecycline and doxycycline can cross the mitochondrial membrane and bind to the 28S subunit, effectively inhibiting protein synthesis and inducing metabolic stress in malignant cells (Source: Lamb et al., 2015, Oncotarget). However, this cross-reactivity also accounts for the mitochondrial toxicity and side effects, such as lactic acidosis and myelosuppression, associated with long-term use of certain antimicrobial agents (Source: Kalghatgi et al., 2013, Science Translational Medicine).

Other names

28S ribosomal subunitmSSUSmall mitochondrial ribosomal subunitMitoribosomal small subunit12S ribosomal subunit

Inhibition of mitochondrial protein translation by binding to the small ribosomal subunit, thereby preventing the assembly of the oxidative phosphorylation complexes.