1. Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases
- Author
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Zuzana Technikova-Dobrova, Sergio Papa, Domenico De Rasmo, Vittoria Petruzzella, Damiano Panelli, Francesco Papa, Giuseppe Palmisano, Anna Maria Sardanelli, Anna Signorile, Antonio Gnoni, Salvatore Scacco, and Loris Micelli
- Subjects
cAMP/PKA pathway ,NDUFS4 ,Biophysics ,Mitochondrial diseases ,Biology ,Biochemistry ,chemistry.chemical_compound ,Structural Biology ,Oxidoreductase ,Complex I ,Cyclic AMP ,Genetics ,Humans ,Genetic Predisposition to Disease ,Phosphorylation ,Molecular Biology ,chemistry.chemical_classification ,Electron Transport Complex I ,Superoxide ,NADH Dehydrogenase ,Cell Biology ,Cyclic AMP-Dependent Protein Kinases ,Respiratory chain complex I ,Cell biology ,Mitochondrial respiratory chain ,chemistry ,Mutation ,Nervous System Diseases ,Signal transduction ,Biogenesis ,Signal Transduction - 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. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
- Published
- 2011