TOKYO, Dec. 31 (Xinhua) -- A Japanese research team recently reported that the onset of reversible infant liver failure is related to a mutation in the gene of an enzyme in the mitochondria, mtu1, which leads to a decrease in its activity. The new discovery is expected to help develop new drugs for this intractable disease.
On April 25, 2022, in the Soa district of the Central Region of Cameroon, parents wait for their child to be given medication. Xinhua News Agency (photo by Copso).
According to a press release jointly issued by Tohoku University, Kumamoto University and the University of Tsukuba in Japan, reversible infant liver failure is a rare pediatric disease with severe liver dysfunction as the main symptom, which generally occurs soon after birth and can cause death. Previous studies have shown that the disease is associated with mutations in the mitochondrial transport ribonucleic acid (TRNA) sulfide-modifying enzyme MTU1, but the pathogenesis at the molecular level is not clear.
This study analyzed 17 previously reported mutations in the MTU1 gene associated with reversible infant liver failure. The researchers first stopped the expression of the MTU1 gene in normal cells, and then introduced 17 MTU1 gene mutations associated with reversible infant liver failure into the cells to cultivate 17 MTU1 gene variant cells, and then studied the catalytic activity of MTU1 on mitochondrial tRNA sulfidation modification in these gene mutant cells and the amount of mutant MTU1 gene synthetase one by one.
The study found that the catalytic activity of this enzyme for mitochondrial tRNA vulcanization modification decreased sharply in cells with the mutant MTU1 gene compared to normal cells, and the synthesis of this enzyme also decreased significantly.
Based on the above findings, the researchers believe that although the enzyme synthesized by the mutant MTU1 gene still retains its activity to a certain extent, due to the overall decrease in activity and synthesis, this enzyme cannot efficiently catalyze the sulfidation modification of mitochondrial tRNA, which further leads to low protein translation level and energy metabolism in mitochondria, and ultimately causes reversible infant liver failure.
Related** has recently been published in the British journal Nucleic Acid Research.