Elongation factor Ts, mitochondrial

TSFM (elongation factor Ts, mitochondrial) is a 325-amino-acid protein that catalyzes GDP-to-GTP exchange on mitochondrial EF-Tu, facilitating aminoacyl-tRNA delivery during mitochondrial protein synthesis (UniProt: P43897). The protein is essential for mitochondrial translation and oxidative phosphorylation complex assembly. Mutations in TSFM cause combined oxidative phosphorylation deficiency 3 (COXPD3), a severe mitochondrial disorder characterized by metabolic acidosis and cardioencephalomyopathy due to defective mitochondrial translation (UniProt: P43897).

TSFM is downregulated in Alzheimer's disease brain tissue relative to age-matched controls (mean log2 fold-change −0.43) based on quantitative proteomics of post-mortem human AD brain across multiple subcellular fractions (Chaparral AD proteomics). This reduction may reflect compromised mitochondrial protein synthesis capacity in AD pathology, consistent with documented bioenergetic dysfunction in Alzheimer's neurons.