The brain‐specific protein, p42^IP4(ADAP 1) is localized in mitochondria and involved in regulation of mitochondrial Ca²⁺

Abstract

We propose that p42 IP4 promotes Ca 2+ -induced permeability transition pore opening and thus destabilizes mitochondria. Keywords: a dual PH domain Arf GAP, brain mitochondria, centaurin-a1, 2¢, 3¢-cyclic nucleotide 3¢-phosphodiesterase, permeability transition pore, a-tubulin.

Calcium-induced permeability transition in rat brain mitochondria is promoted by carbenoxolone through targeting connexin43

“…Isolated RBM were subjected to fractionation by methods described previously (18). Briefly, RBM were subjected to swelling by the addition of buffer (10 mM KH2PO4, pH 7.4) containing a cocktail of protease inhibitors and were incubated for 20 min at 4°C with gentle mixing.…”

“…The outer membranes and mitoplast pellets were solubilized in lysis buffer containing protease inhibitors, which are described above. The purity of the fraction was checked by Western blot analysis, using markers for the compartment-specific proteins as described before (18). Membranes were stained by antivoltage-dependent anion channel (VDAC; porin) antibody (outer membrane), anti-cytochrome c antibody (intermembrane space), and anti-COX antibody (inner membrane), as well as anti-Mn-superoxide dismutase (SOD) antibody (mitoplasts).…”

“…To examine the localization of Cx43 in mitochondria, submitochondrial fractions were isolated from RBM (outer membrane, intermembrane space, and mitoplasts, containing the inner membrane with matrix). The purity of mitochondrial subfractions was checked with antibodies for specific marker proteins of the outer membrane (VDAC), intermembrane space (cytochrome c), the inner membrane (COX), and matrix (SOD-2), as we reported previously (18). The Western blot of the mitochondrial subfractions from RBM in Fig.…”

Tubulin potentiates the interaction of the metalloendopeptidase nardilysin with the neuronal scaffold protein p42IP4/centaurin-α1 (ADAP1)

“…p42 IP4 has been demonstrated to interact with α-tubulin (Galvita et al 2009). Taken together, these findings have prompted us to determine (1) whether NRD, p42 IP4 and tubulin colocalize in live cells in culture, (2) whether the disturbance of tubulin polymerization in vivo affects the localization of these proteins and (3) whether the interaction of p42 IP4 with NRD is functionally promoted by tubulin.…”

“…Our latest reports on p42 IP4 demonstrate a localization of the protein p42 IP4 in the inter-membrane space of mitochondria (Galvita et al 2009), interacting with the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein that is strongly involved in myelination and that also interacts with α-tubulin (Bifulco et al 2002).…”