title: Dysfunction of mitochondrial respiratory chain complex I in neurological disorders: genetics and pathogenetic mechanisms.
abstract: This chapter covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in neurological disorders associated with complex I defects. Complex I formation and functionality in mammalian cells depends on coordinated expression of nuclear and mitochondrial genes, post-translational subunit modifications, mitochondrial import/maturation of nuclear encoded subunits, subunits interaction and stepwise assembly, and on proteolytic processing. Examples of complex I dysfunction are herein presented: homozygous mutations in the nuclear NDUFS1 and NDUFS4 genes for structural components of complex I; an autosomic recessive form of encephalopathy associated with enhanced proteolytic degradation of complex I; familial cases of Parkinson associated to mutations in the PINK1 and Parkin genes, in particular, homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex I, coexistent with mutation in the PINK1 gene. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in neurological disorders, as well as for developing therapeutical strategies.
authors.affiliation: Department of Basic Medical Sciences, University of Bari, Policlinico, Bari, Italy.
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Damiano
authors.initials: D
authors.lastname: Panelli
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Raffaella
authors.initials: R
authors.lastname: Trentadue
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
mesh_terms: D004579:Electron Transport; D042967:Electron Transport Complex I / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009422:Nervous System Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D010375:Pedigree
chemical_list: D042967:Electron Transport Complex I