Ferrer-Cortès Xènia, Narbona Juan, Bujan Núria, Matalonga Leslie, Del Toro Mireia, Arranz José Antonio, Riudor Encarnació, Garcia-Cazorla Angels, Jou Cristina, O'Callaghan Mar, Pineda Mercé, Montero Raquel, Arias Angela, García-Villoria Judit, Alston Charlotte L, Taylor Robert W, Briones Paz, Ribes Antonia, Tort Frederic
Hospital Clínic, IDIBAPS, CIBERER, Barcelona, Spain.
Clinica Universitária de Navarra, Facultad Medicina, Pamplona, Spain.
Mitochondrion. 2016 Jan;26:72-80. doi: 10.1016/j.mito.2015.12.004. Epub 2015 Dec 11.
Mutations in NFU1 were recently identified in patients with fatal encephalopathy. NFU1 is an iron-sulfur cluster protein necessary for the activity of the mitochondrial respiratory chain complexes I-II and the synthesis of lipoic acid. We report two NFU1 compound heterozygous individuals with normal complex I and lipoic acid-dependent enzymatic activities and low, but detectable, levels of lipoylated proteins. We demonstrated a leaky splicing regulation due to a splice site mutation (c.545+5G>A) that produces small amounts of wild type NFU1 mRNA that might result in enough protein to partially lipoylate and restore the activity of lipoic acid-dependent enzymes and the assembly and activity of complex I. These results allowed us to gain insights into the molecular basis underlying this disease and should be considered for the diagnosis of NFU1 patients.
最近在患有致命性脑病的患者中发现了NFU1突变。NFU1是一种铁硫簇蛋白，对于线粒体呼吸链复合体I-II的活性以及硫辛酸的合成是必需的。我们报告了两名NFU1复合杂合个体，他们的复合体I和硫辛酸依赖性酶活性正常，硫辛酰化蛋白水平较低但可检测到。我们证明了由于剪接位点突变（c.545+5G>A）导致的剪接调控缺陷，该突变产生少量野生型NFU1 mRNA，这可能会产生足够的蛋白质来部分硫辛酰化并恢复硫辛酸依赖性酶的活性以及复合体I的组装和活性。这些结果使我们能够深入了解该疾病的分子基础，并且在NFU1患者的诊断中应予以考虑。
