TY - JOUR
T1 - Respiratory chain complex I, a main regulatory target of the cAMP/PKA pathway is defective in different human diseases
AU - Papa, Sergio
AU - Rasmo, Domenico De
AU - Technikova-Dobrova, Zuzana
AU - Panelli, Damiano
AU - Signorile, Anna
AU - Scacco, Salvatore
AU - Petruzzella, Vittoria
AU - Papa, Francesco
AU - Palmisano, Giuseppe
AU - Gnoni, Antonio
AU - Micelli, Loris
AU - Sardanelli, Anna Maria
PY - 2012/3/9
Y1 - 2012/3/9
N2 - 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.
AB - 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.
KW - cAMP/PKA pathway
KW - Complex I
KW - Mitochondrial diseases
KW - NDUFS4
UR - http://www.scopus.com/inward/record.url?scp=84857918871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857918871&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2011.09.019
DO - 10.1016/j.febslet.2011.09.019
M3 - Article
C2 - 21945319
AN - SCOPUS:84857918871
SN - 0014-5793
VL - 586
SP - 568
EP - 577
JO - FEBS Letters
JF - FEBS Letters
IS - 5
ER -