Chatfield Kathryn C, Coughlin Curtis R, Friederich Marisa W, Gallagher Renata C, Hesselberth Jay R, Lovell Mark A, Ofman Rob, Swanson Michael A, Thomas Janet A, Wanders Ronald J A, Wartchow Eric P, Van Hove Johan L K
Pediatric Cardiology, Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO, USA.
Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO, USA.
Mitochondrion. 2015 Mar;21:1-10. doi: 10.1016/j.mito.2014.12.005. Epub 2015 Jan 6.
Muscle, heart and liver were analyzed in a male subject who succumbed to HSD10 disease. Respiratory chain enzyme analysis and BN-PAGE showed reduced activities and assembly of complexes I, III, IV, and V. The mRNAs of all RNase P subunits were preserved in heart and overexpressed in muscle, but MRPP2 protein was severely decreased. RNase P upregulation correlated with increased expression of mitochondrial biogenesis factors and preserved mitochondrial enzymes in muscle, but not in heart where this compensatory mechanism was incomplete. We demonstrate elevated amounts of unprocessed pre-tRNAs and mRNA transcripts encoding mitochondrial subunits indicating deficient RNase P activity. This study provides evidence of abnormal mitochondrial RNA processing causing mitochondrial energy failure in HSD10 disease.
对一名死于HSD10疾病的男性受试者的肌肉、心脏和肝脏进行了分析。呼吸链酶分析和蓝色天然聚丙烯酰胺凝胶电泳显示复合物I、III、IV和V的活性和组装减少。所有核糖核酸酶P亚基的信使核糖核酸在心脏中得以保留，在肌肉中过度表达，但MRPP2蛋白严重减少。核糖核酸酶P上调与肌肉中线粒体生物发生因子表达增加和线粒体酶保留相关，但在心脏中这种补偿机制不完整。我们证明未加工的前体转运核糖核酸和编码线粒体亚基的信使核糖核酸转录本数量增加，表明核糖核酸酶P活性不足。本研究提供了证据，证明异常的线粒体核糖核酸加工导致HSD10疾病中的线粒体能量衰竭。
