Mammalian complex I: a regulable and vulnerable pacemaker in mitochondrial respiratory function.
In this paper the regulatory features of complex I of mammalian and human mitochondria are reviewed. In a variety of mitotic cell-line cultures, activation in vivo of the cAMP cascade, or direct addition of cAMP, promotes the NADH-ubiquinone oxidoreductase activity of complex I and lower the cellular level of ROS. These effects of cAMP are found to be associated with PKA-mediated serine phosphorylation in the conserved C-terminus of the subunit of complex I encoded by the nuclear gene NDUFS4. PKA mediated phosphorylation of this Ser in the C-terminus of the protein promotes its mitochondrial import and maturation. Mass-spectrometry analysis of the phosphorylation pattern of complex I subunits is also reviewed.
Papa
Sergio
S
Department of Medical Biochemistry, Biology and Physics (DIBIFIM), University of Bari, Italy. papabchm@cimedoc.uniba.it
De Rasmo
Domenico
D
Scacco
Salvatore
S
Signorile
Anna
A
Technikova-Dobrova
Zuzana
Z
Palmisano
Giuseppe
G
Sardanelli
Anna Maria
AM
Papa
Francesco
F
Panelli
Damiano
D
Scaringi
Raffaella
R
Santeramo
Arcangela
A
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D000242:Cyclic AMP / Q000378:metabolism; D042967:Electron Transport Complex I / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis; D007700:Kinetics; D008322:Mammals; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010101:Oxygen Consumption; D017386:Sequence Homology, Amino Acid
D000242:Cyclic AMP; D042967:Electron Transport Complex I