Japanese scholars have constructed the first mouse model carrying mitochondrial tRNALeu mutations

Studying the role of mitochondria in metabolic diseases has been difficult because of the lack of animal models with specific mitochondrial mutations to look at these tiny organelles

Recently, a team of researchers at the University of Tsukuba in Japan constructed the first mouse model carrying disease-associated mitochondrial tRNA Leu mutations, and showed that the resulting disease was caused

Mitochondria are surrounded by two membranes and contain a small amount of their own DNA

Researchers at the University of Tsukuba fused cells in mitochondria that carry mutant DNA but no nucleus with embryonic stem cells that used the drug rhodamine 6G to remove all mitochondria, creating a mouse model

The A2748G mutation is homologous to the A3302G mutation in human patients, which is one of the most common mutations in the mitochondria associated with certain human diseases, including neuromuscular diseases, brain damage, and metabolic disorders

Mice carrying the A2748G mutation developed metabolic disorders whose symptoms were similar

Corresponding author Professor Kazuto Nakada of the University of Tsukuba explains: "Misprocessing of RNA containing the A2748G mutation has led to reduced translation of a protein called ND1, a component

The resulting complex I defect affects the function of the cellular energy production pathway, which in turn leads to mitochondrial dysfunction and metabolic disorders

Journal Reference:

Haruna Tani, Kaori Ishikawa, Hiroaki Tamashiro, Emi Ogasawara, Takehiro Yasukawa, Shigeru Matsuda, Akinori Shimizu, Dongchon Kang, Jun-Ichi Hayashi, Fan-Yan Wei, Kazuto Nakada.