Target intelligence / Profile preview

Mitochondrial 28S ribosomal subunit (28S mitoribosomal subunit)

Target
28S mitoribosomal subunit
Molecular classification
Riboprotein complex, Ribosome subunit
01

Overview

The Mitochondrial 28S ribosomal subunit (also known as the small mitoribosomal subunit or 30S-like subunit) is a ribonucleoprotein complex essential for the synthesis of the 13 proteins encoded by the mitochondrial genome (Greber & Ban, 2016). These proteins are critical components of the oxidative phosphorylation (OXPHOS) system, which generates the majority of cellular ATP (Hällberg & Larsson, 2014). Due to its evolutionary descent from bacterial ancestors, the 28S subunit shares structural homology with the bacterial 30S subunit, making it a frequent off-target for antibiotics such as aminoglycosides and tetracyclines (Kohanski et al., 2010). This cross-reactivity is a primary cause of drug-induced toxicities, including permanent hearing loss and kidney damage, particularly in individuals carrying specific mitochondrial DNA mutations like m.1555A>G (Guan, 2011). Beyond toxicity, the 28S subunit is an emerging therapeutic target in oncology; certain malignancies, including acute myeloid leukemia, demonstrate a heightened reliance on mitochondrial translation, suggesting that selective inhibition of the mitoribosome could serve as an effective anti-cancer strategy (Skrtic et al., 2011).

Other names
Mitochondrial 30S ribosomal subunitSmall mitochondrial ribosomal subunit28S mitoribosomal subunitmS subunitMitoribosomal small subunit12S rRNA-protein complex
02

Mechanism of action

Inhibition of mitochondrial protein synthesis by binding to the 12S rRNA A-site, leading to translational misreading or termination (Kohanski et al., 2010).

03

Biological functions

Mitochondrial translationProtein synthesisOxidative phosphorylation regulationMetabolic homeostasis
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Disease associations

CancerMitochondrial diseaseAminoglycoside-induced ototoxicityNephrotoxicityLeigh syndrome
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Safety considerations

Ototoxicity (permanent hearing loss)NephrotoxicityLactic acidosisMitochondrial dysfunctionMyelosuppression
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Interacting drugs

Gentamicin

9 more in the full profile.

07

Biomarkers

MT-RNR1 m.1555A>G mutationMT-RNR1 m.1494C>T mutationMitochondrial protein synthesis rateOXPHOS protein levels

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