Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases

Sergio Papa, Domenico De Rasmo, Zuzana Technikova-Dobrova, Damiano Panelli, Anna Signorile, Salvatore Scacco, Vittoria Petruzzella, Francesco Papa, Giuseppe Palmisano, Antonio Gnoni, Loris Micelli, Anna Maria Sardanelli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)568-577
Number of pages10
JournalFEBS Letters
Volume586
Issue number5
DOIs
Publication statusPublished - Mar 9 2012

Keywords

  • cAMP/PKA pathway
  • Complex I
  • Mitochondrial diseases
  • NDUFS4

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology
  • Genetics
  • Molecular Biology
  • Structural Biology

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