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Abstract

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.

Carbenoxolone induces permeability transition pore opening in rat mitochondria via the translocator protein TSPO and connexin43

“…The molecular mass of the phosphorylated proteins is 43–46 kDa (where Cx43 was found), 17 kDa and 21.5 kDa (identified by 2D electrophoresis and mass spectrometry analysis as phosphorylated isoforms of MBP associated with mitochondria [28]), 3.5 kDa (identified as subunit c of FoF 1 -ATP synthase [29]). Modulation of the phosphorylation level of these proteins is Ca 2+ - and CsA-dependent, supporting their relationship with mPTP function [26,31,32,46]. Interestingly, while Cbx lowers threshold calcium concentration in purified synaptic and non-synaptic mitochondria, in the present study we found acceleration of mPTP opening in non-purified RBM without changing of threshold calcium.…”

“…ANT, being a part of the ATP synthasome, can contact subunit c of the Fo-ATP synthase [51,52]. Thus, the phosphorylation status of subunit c coupled with its pore forming properties [32,46] can be modulated. It is also likely that PAP7/ACBD3 might bind phosphodiesterase as an anchoring protein.…”

Inhibition of Bcl-xL prevents pro-death actions of ΔN-Bcl-xL at the mitochondrial inner membrane during glutamate excitotoxicity

“…ATP synthase is an important candidate to form mPTP. 14 , 36 , 37 , 38 , 39 , 40 We and other have previously suggested that the c-subunit of the ATP synthase forms the mPTP. 14 , 36 To determine if ΔN-Bcl-xL plays a role in activation of mPTP during glutamate toxicity, we asked if depletion of the ATP synthase c-subunit prevents mitochondrial inner membrane depolarization and neuronal death caused by glutamate toxicity.…”

Role of the c subunit of the FOATP synthase in mitochondrial permeability transition

“…46,47 Moreover, (1) the c, but not the b, subunit has been ascribed with conductive properties; 48 and (2) a peptide displaying a consistent degree of similarity to the c subunit has been indicated as a putative regulator of the PTPC. 49 Therefore, we focused on the putative contribution of the c subunit of the F O ATP synthase to the lethal functions of the PTPC.…”