Human mitochondrial ribosome large subunit peptidyl transferase center (mitoribosomal PTC)

The human mitochondrial ribosome large subunit peptidyl transferase center (PTC) is the catalytic core of the 39S mitoribosomal subunit, primarily composed of the 16S ribosomal RNA (MT-RNR2) [PMID: 25888244]. Its fundamental biological role is to catalyze the formation of peptide bonds during the translation of the 13 essential proteins encoded by the mitochondrial genome, which are critical components of the oxidative phosphorylation system [PMID: 33053377]. While primarily a target for certain classes of antibiotics like oxazolidinones (e.g., linezolid) and chloramphenicol, its structural similarity to bacterial ribosomes leads to off-target mitochondrial toxicity [PMID: 12811358]. This toxicity often manifests clinically as myelosuppression, lactic acidosis, or neuropathies due to impaired mitochondrial protein synthesis [PMID: 22585461]. Recently, the PTC has emerged as a potential therapeutic target in oncology, as many cancer cells, particularly in acute myeloid leukemia, exhibit an increased reliance on mitochondrial biogenesis to support rapid proliferation [PMID: 22099511]. Understanding the structural nuances of the human mitoribosomal PTC is essential for developing drugs that can either selectively target bacterial ribosomes to avoid toxicity or specifically inhibit mitochondrial function in malignant cells [PMID: 25888244].

Other names

39S ribosomal subunit peptidyl transferase centerMitochondrial 16S rRNA peptidyl transferase centerMitoribosomal PTCLarge mitoribosomal subunit catalytic centerMT-RNR2 peptidyl transferase center

Inhibition of mitochondrial protein synthesis by binding to the peptidyl transferase center and preventing peptide bond formation or the translocation of the growing polypeptide chain [PMID: 12811358, PMID: 25888244].