title: Pathogenetic mechanisms in hereditary dysfunctions of complex I of the respiratory chain in neurological diseases.
abstract: 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.
authors.affiliation: Department of Medical Biochemistry, Biology and Physics, University of Bari, Italy. papabchm@cimedoc.uniba.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
authors.forename: Arcangela
authors.initials: A
authors.lastname: Iuso
authors.forename: Damiano
authors.initials: D
authors.lastname: Panelli
authors.forename: Rita
authors.initials: R
authors.lastname: Vitale
authors.forename: Raffaella
authors.initials: R
authors.lastname: Trentadue
authors.forename: Domenico
authors.initials: D
authors.lastname: De Rasmo
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Capitanio
authors.forename: Claudia
authors.initials: C
authors.lastname: Piccoli
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Michele
authors.initials: M
authors.lastname: Scivetti
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Teresa
authors.initials: T
authors.lastname: Rizza
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Michele
mesh_terms: D000595:Amino Acid Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D042967:Electron Transport Complex I / Q000737:chemistry / Q000235:genetics*; D004827:Epilepsy / Q000201:enzymology / Q000235:genetics; D006801:Humans; D017237:Mitochondrial Encephalomyopathies / Q000201:enzymology / Q000235:genetics; D008958:Models, Molecular; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics; D009422:Nervous System Diseases / Q000201:enzymology* / Q000235:genetics*; D010300:Parkinson Disease / Q000201:enzymology / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; C487793:NDUFS1 protein, human; D017382:Reactive Oxygen Species; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human