Phosphorylation of a peptide related to subunit c of the F0F1-ATPase/ATP synthase and relationship to permeability transition pore opening in mitochondria.
A phosphorylated polypeptide (ScIRP) from the inner membrane of rat liver mitochondria with an apparent molecular mass of 3.5 kDa was found to be immunoreactive with specific antibodies against subunit c of F0F1-ATPase/ATP synthase (Azarashvily, T. S., Tyynelä, J., Baumann, M., Evtodienko, Yu. V., and Saris, N.-E. L. (2000). Biochem. Biophys. Res. Commun. 270, 741-744. In the present paper we show that the dephosphorylation of ScIRP was promoted by the Ca2+-induced mitochondrial permeability transition (MPT) and prevented by cyclosporin A. Preincubation of ScIRP isolated in its dephosphorylated form with the mitochondrial suspension decreased the membrane potential (delta psiM) and the Ca2+-uptake capacity by promoting MPT. Incorporation of ScIRP into black-lipid membranes increased the membrane conductivity by inducing channel formation that was also suppressed by antibodies to subunit c. These data indicate that the phosphorylation level of ScIRP is influenced by the MPT pore state, presumably by stimulation of calcineurin phosphatase by the Ca2+ used to induce MPT. The possibility of ScIRP being part of the MPT pore assembly is discussed in view of its capability to induced channel activity.
Azarashvili
Tamara S
TS
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region.
Tyynelä
Jaana
J
Odinokova
Irina V
IV
Grigorjev
Pavel A
PA
Baumann
Marc
M
Evtodienko
Yuri V
YV
Saris
Nils-Erik L
NE
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D007425:Intracellular Membranes / Q000737:chemistry* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D008930:Mitochondria, Liver / Q000648:ultrastructure*; D010455:Peptides / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology*; D010539:Permeability; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits; D006180:Proton-Translocating ATPases; D051381:Rats; D017208:Rats, Wistar
D010455:Peptides; D021122:Protein Subunits; D016572:Cyclosporine; D006180:Proton-Translocating ATPases; D002118:Calcium