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Pathogenetic mechanisms in hereditary dysfunctions of complex I of the respiratory chain in neurological diseases

2009; Elsevier BV; Volume: 1787; Issue: 5 Linguagem: Inglês

10.1016/j.bbabio.2008.12.018

1879-2650

Sergio Papa, Vittoria Petruzzella, Salvatore Scacco, Anna Maria Sardanelli, Arcangela Iuso, Damiano Panelli, Rita Vitale, R Trentadue, Domenico De Rasmo, Nazzareno Capitanio, Cláudia Piccoli, Francesco Papa, Michele Scivetti, Enrico Bertini, Teresa Rizza, Giuseppe De Michele,

Neuroscience of respiration and sleep

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, cohexistent 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.