Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria

Abstract

Rat heart mitochondria became permeabilized to sucrose when incubated with 100 nmol of Ca2+/mg of protein in the presence of Pi. Ca2+ chelation with EGTA restored impermeability to sucrose, which became entrapped in the matrix space. t-Butylhydroperoxide markedly promoted permeabilization in the presence of Ca2+ but not in its absence, and Ca2+-plus-t-butylhydroperoxide-induced permeabilization was reversed by EGTA. The data suggest that Ca2+ and oxidative stress synergistically promote the reversible opening of an inner membrane pore.

Complexes between kinases, mitochondrial porin and adenylate translocator in rat brain resemble the permeability transition pore

“…2B). The observed conductance is comparable to that of a mitochondrial channel described by Kinally [21] and Zoratti [22] that appeared to be identical [22] with the cyclosporin A sensitive permeability transition pore [23,24]. In agreement with this thought was the arresting of the channel in the open state and the reduction of voltage sensitivity of pore conductance by atractyloside.…”

“…4A) the release of malate by 500 gM Ca 2+ could be inhibited through the activity of hexokinase with 5 mM glucose and 0.2 mM ATP. N-MethylVal-cyclosporin is a derivative of cyclosporin A that has been characterised as a specific inhibitor of the permeability transition pore [22][23][24][25][26][27][28][29][30]. N-MethylVal-cyclosporin binds to the mitochon- (Fig.…”

Calcineurin and mitochondrial function in glutamate‐induced neuronal cell death

“…Therefore, we decided to investigate whether the observed disturbance of the mitochondrial membrane potential during excitotoxicity was associated with mitochondrial permeability transition. For these studies we used cyclosporin A (CsA), which prevents the opening of the proteinaceous pore [17][18][19]. However, cyclosporin A, in complex with the immunophilin, cyclophilin, is also a potent inhibitor of the Ca2+/ calmodulin-regulated protein phosphatase, calcineurin [20].…”

Identification and purification of a bovine liver mitochondrial NAD+‐glycohydrolase

“…This localization is quite controversial as it would call into question the role of NAD ÷-glycohydrolase in the hydrolysis of intramitochondrial pyridine nucleotides. In case of a localization in the outer membrane NAD + could only be hydrolysed after its release through an inner membrane pore, Formation of such pores has been observed upon oxidative stress [10]. However, their involvement in NAD ÷ hydrolysis appears unlikely, because pore formation is not required for the hydroperoxide-induced Ca 2+ release from rat liver mitochondria [11].…”