Lane Maria, Boczonadi Veronika, Bachtari Sahar, Gomez-Duran Aurora, Langer Thorsten, Griffiths Alexandra, Kleinle Stephanie, Dineiger Christine, Abicht Angela, Holinski-Feder Elke, Schara Ulrike, Gerner Patrick, Horvath Rita
Institute of Genetic Medicine, John Walton Muscular Dystrophy Research Centre and Wellcome Trust Centre for Mitochondrial Research, Central Parkway, NE1 3BZ, Newcastle upon Tyne, UK.
Department of Paediatric Gastroenterology, University of Duisburg-Essen, Essen, Germany.
J Inherit Metab Dis. 2016 May;39(3):427-436. doi: 10.1007/s10545-016-9927-z. Epub 2016 Apr 6.
Liver failure is a heterogeneous condition which may be fatal and the primary cause is frequently unknown. We investigated mitochondrial oxidative phosphorylation in patients undergoing liver transplantation. We studied 45 patients who had liver transplantation due to a variety of clinical presentations. Blue native polyacrylamide gel electrophoresis with immunodetection of respiratory chain complexes I-V, biochemical activity of respiratory chain complexes II and IV and quantification of mitochondrial DNA (mtDNA) copy number were investigated in liver tissue collected from the explanted liver during transplantation. Abnormal mitochondrial function was frequently present in this cohort: ten of 40 patients (25 %) had a defect of one or more respiratory chain enzyme complexes on blue native gels, 20 patients (44 %) had low activity of complex II and/or IV and ten (22 %) had a reduced mtDNA copy number. Combined respiratory chain deficiency and reduced numbers of mitochondria were detected in all three patients with acute liver failure. Low complex IV activity in biliary atresia and complex II defects in cirrhosis were common findings. All six patients diagnosed with liver tumours showed variable alterations in mitochondrial function, probably due to the heterogeneity of the presenting tumour. In conclusion, mitochondrial dysfunction is common in severe liver failure in non-mitochondrial conditions. Therefore, in contrast to the common practice detection of respiratory chain abnormalities in liver should not restrict the inclusion of patients for liver transplantation. Furthermore, improving mitochondrial function may be targeted as part of a complex therapy approach in different forms of liver diseases.
肝衰竭是一种异质性疾病，可能致命，且主要病因常常不明。我们对接受肝移植的患者的线粒体氧化磷酸化进行了研究。我们研究了45例因各种临床表现而接受肝移植的患者。在移植过程中从切除的肝脏收集的肝组织中，采用蓝色天然聚丙烯酰胺凝胶电泳结合呼吸链复合体I-V的免疫检测、呼吸链复合体II和IV的生化活性以及线粒体DNA（mtDNA）拷贝数的定量分析。该队列中经常出现线粒体功能异常：40例患者中有10例（25%）在蓝色天然凝胶上存在一种或多种呼吸链酶复合体缺陷，20例患者（44%）复合体II和/或IV活性低，10例（22%）mtDNA拷贝数减少。在所有3例急性肝衰竭患者中均检测到呼吸链联合缺陷和线粒体数量减少。胆道闭锁患者复合体IV活性低以及肝硬化患者复合体II缺陷是常见发现。所有6例被诊断为肝肿瘤的患者线粒体功能均有不同程度改变，可能是由于所呈现肿瘤的异质性。总之，在非线粒体疾病导致的严重肝衰竭中，线粒体功能障碍很常见。因此，与常规做法不同，在肝脏中检测呼吸链异常不应限制肝移植患者的纳入。此外，改善线粒体功能可作为不同形式肝病综合治疗方法的一部分。
