title: Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases.
abstract: In mammals, complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain has 31 supernumerary subunits in addition to the 14 conserved from prokaryotes to humans. Multiplicity of structural protein components, as well as of biogenesis factors, makes complex I a sensible pace-maker of mitochondrial respiration. The work reviewed here shows that the cAMP/PKA pathway regulates the biogenesis, assembly and catalytic activity of complex I and mitochondrial oxygen superoxide production. The structural, functional and regulatory complexity of complex I, renders it particularly vulnerable to genetic and sporadic pathological factors. Complex I dysfunction has, indeed, been found, to be associated with several human diseases. Knowledge of the pathogenetic mechanisms of these diseases can help to develop new therapeutic strategies.
authors.affiliation: Department of Basic Medical Sciences, Section of Medical Biochemistry, University of Bari Aldo Moro, Bari, Italy. s.papa@biochem.uniba.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Papa
authors.forename: Domenico De
authors.initials: DD
authors.lastname: Rasmo
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Technikova-Dobrova
authors.forename: Damiano
authors.initials: D
authors.lastname: Panelli
authors.forename: Anna
authors.initials: A
authors.lastname: Signorile
authors.forename: Salvatore
authors.initials: S
authors.lastname: Scacco
authors.forename: Vittoria
authors.initials: V
authors.lastname: Petruzzella
authors.forename: Francesco
authors.initials: F
authors.lastname: Papa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmisano
authors.forename: Antonio
authors.initials: A
authors.lastname: Gnoni
authors.forename: Loris
authors.initials: L
authors.lastname: Micelli
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Sardanelli
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D000242:Cyclic AMP; D009245:NADH Dehydrogenase; D017868:Cyclic AMP-Dependent Protein Kinases; D042967:Electron Transport Complex I; C427643:NDUFS4 protein, human