Elongation factor Ts, mitochondrial (TSFM)

Elongation factor Ts, mitochondrial (TSFM) is a nuclear-encoded mitochondrial enzyme required for the elongation phase of protein translation in mitochondria. It acts as a guanine nucleotide exchange factor for elongation factor Tu (EF-Tu), facilitating the recycling of GDP for GTP during translation. TSFM remains transiently associated with the aminoacyl-tRNA.EF-Tu.GTP complex, ensuring efficient peptide elongation on the mitochondrial ribosome. Mutations in TSFM cause rare but severe early-onset mitochondrial disorders, including combined oxidative phosphorylation deficiency, mitochondrial encephalopathies, and cardiomyopathies. There are several splice isoforms, but all share the catalytically important N-terminal region. Pathogenic mutations destabilize the EF-Ts/EF-Tu complex, impairing mitochondrial translation and causing tissue-specific disease phenotypes, predominantly in the heart and nervous system. No approved drugs target TSFM, and therapeutic intervention is highly challenging due to its essential role in mitochondrial protein synthesis and cell viability.

Other names

Ts translation elongation factor, mitochondrialEF-TsEF-TsMtEF-TsmtEF-TSEFTSEFTSMTTs translation elongation factorEFTS ProteinP43897 (UniProt)

For interacting compounds such as kirromycin, the mechanism involves perturbing the conformational relationship between EF-Tu and EF-Ts, affecting nucleotide exchange. In general, TSFM activity is essential for mitochondrial protein translation, so any inhibitor would block mitochondrial protein synthesis by preventing GDP/GTP exchange on EF-Tu.