Papa Sergio, Petruzzella Vittoria, Scacco Salvatore, Sardanelli Anna Maria, Iuso Arcangela, Panelli Damiano, Vitale Rita, Trentadue Raffaella, De Rasmo Domenico, Capitanio Nazzareno, Piccoli Claudia, Papa Francesco, Scivetti Michele, Bertini Enrico, Rizza Teresa, De Michele Giuseppe
Department of Medical Biochemistry, Biology and Physics, University of Bari, Italy.
Biochim Biophys Acta. 2009 May;1787(5):502-17. doi: 10.1016/j.bbabio.2008.12.018. Epub 2009 Jan 10.
This paper covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in hereditary neurological disorders associated with complex I defects. Three types of hereditary complex I dysfunction are dealt with: (i) homozygous mutations in the nuclear genes NDUFS1 and NDUFS4 of complex I, associated with mitochondrial encephalopathy; (ii) a recessive hereditary epileptic neurological disorder associated with enhanced proteolytic degradation of complex I; (iii) homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex, coexistent with mutation in the nuclear PINK1 gene in familial Parkinsonism. The genetic and biochemical data examined highlight different mechanisms by which mitochondrial bioenergetics is altered in these hereditary defects of complex I. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in sporadic neurological disorders and aging, as well as for developing therapeutical strategies.
本文涵盖了与复合体I缺陷相关的遗传性神经疾病中线粒体生物能量学功能障碍的遗传和生化方面。文中探讨了三种类型的遗传性复合体I功能障碍：（i）复合体I的核基因NDUFS1和NDUFS4中的纯合突变，与线粒体脑病相关；（ii）一种隐性遗传性癫痫性神经疾病，与复合体I的蛋白水解降解增强有关；（iii）复合体的线粒体基因ND5和ND6中的同质性突变，与家族性帕金森病中的核PINK1基因突变共存。所研究的遗传和生化数据突出了在这些复合体I遗传性缺陷中线粒体生物能量学发生改变的不同机制。这些知识除了阐明遗传性疾病发病机制的分子方面外，还可为理解复合体I在散发性神经疾病和衰老中的作用提供线索，以及为制定治疗策略提供帮助。
