Elongation factor Tu, mitochondrial

Elongation factor Tu, mitochondrial (TUFM) is a GTP hydrolase essential for mitochondrial protein synthesis, catalyzing the GTP-dependent binding of aminoacyl-tRNA to ribosomal A-sites (UniProt: P49411). Beyond translation, TUFM regulates autophagy and innate immunity by recruiting ATG5-ATG12 and NLRX1 complexes at mitochondria, thereby modulating the RLR-MAVS signaling pathway to suppress type I interferon while promoting autophagy (UniProt: P49411).

Mutations in TUFM cause combined oxidative phosphorylation deficiency 4 (COXPD4), a severe mitochondrial disease characterized by neonatal lactic acidosis, progressive encephalopathy, and impaired mitochondrial protein synthesis (UniProt: P49411). This disease context highlights TUFM's critical role in maintaining mitochondrial function and bioenergetics.

In Alzheimer's disease, TUFM shows ambiguous regulation across subcellular fractions in human post-mortem AD brain compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change of 0.54 suggests modest upregulation overall, though this direction is inconsistent across the two fractions examined in the TMT-labeled quantitative proteomics study, limiting definitive conclusions about TUFM's role in AD pathology.