Beschreibung:
<jats:title>Abstract</jats:title><jats:p>Inborn errors of metabolism are related to mitochondrial disorders caused by dysfunction of the oxidative phosphorylation (OXPHOS) system. Congenital hypermetabolism in the infant is a rare disease belonging to Luft syndrome, nonthyroidal hypermetabolism, arising from a singular example of a defect in OXPHOS. The mitochondria lose coupling of mitochondrial substrates oxidation from the ADP phosphorylation. Since Luft syndrome is due to uncoupled cell respiration responsible for deficient in ATP production that originates in the respiratory complexes, a de novo heterozygous variant in the catalytic subunit of mitochondrial F<jats:sub>1</jats:sub>F<jats:sub>O</jats:sub>‐ATPase arises as the main cause of an autosomal dominant syndrome of hypermetabolism associated with dysfunction in ATP production, which does not involve the respiratory complexes. The F<jats:sub>1</jats:sub>F<jats:sub>O</jats:sub>‐ATPase works as an embedded molecular machine with a rotary action using two different motor engines. The F<jats:sub>O</jats:sub>, which is an integral domain in the membrane, dissipates the chemical potential difference for H<jats:sup>+</jats:sup>, a proton motive force (Δ<jats:italic>p</jats:italic>), across the inner membrane to generate a torsion. The F<jats:sub>1</jats:sub> domain—the hydrophilic portion responsible for ATP turnover—is powered by the molecular rotary action to synthesize ATP. The structural and functional coupling of F<jats:sub>1</jats:sub> and F<jats:sub>O</jats:sub> domains support the energy transduction for ATP synthesis. The dissipation of Δ<jats:italic>p</jats:italic> by means of an H<jats:sup>+</jats:sup> slip correlated to rotor free‐wheeling of the F<jats:sub>1</jats:sub>F<jats:sub>O</jats:sub>‐ATPase has been discovered to cause enzyme dysfunction in primary mitochondrial disorders. In this insight, we try to offer commentary and analysis of the molecular mechanism in these impaired mitochondria.</jats:p>