Gene of the Month – October: ATP5F1B
The researchers detected the de novo variant in ATP5F1B in monozygotic twins. The two boys did not gain weight despite excessive caloric intake. They showed tachypnea, intermittent hyperthermia and euthyroid hypermetabolism. Investigations performed on patient fibroblasts and CRISPR/Cas9-engineered cellular models revealed decreased mitochondrial membrane potential and elevated oxygen consumption. The authors suggest that ATP5F1B dysfunction leads to greater flux of protons through complex V and less efficient ATP production. ATP5F1B forms a subunit of mitochondrial ATP synthase. This enzyme complex, which is also called complex V, is essential in mitochondrial oxidative phosphorylation and uses the proton gradient across the membrane to produce ATP.
Ganetzky RD, Markhard AL, Yee I, …, Mootha VK. Congenital Hypermetabolism and Uncoupled Oxidative Phosphorylation. N Engl J Med. 2022 Oct 13;387(15):1395-1403. doi: 10.1056/NEJMoa2202949.