Effects of extramitochondrial ADP on permeability transition of mouse liver mitochondria

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Abstract

Carboxyatractylate (CAT) and atractylate inhibit the mitochondrial adenine nucleotide translocator (ANT) and stimulate the opening of permeability transition pore (PTP). Following pretreatment of mouse liver mitochondria with 5 μM CAT and 75 μM Ca 2+, the activity of PTP increased, but addition of 2 mM ADP inhibited the swelling of mitochondria. Extramitochondrial Ca 2+ concentration measured with Calcium-Green 5N evidenced that 2 mM ADP did not remarkably decrease the free Ca 2+ but the release of Ca 2+ from loaded mitochondria was stopped effectively after addition of 2 mM ADP. CAT caused a remarkable decrease of the maximum amount of calcium ions, which can be accumulated by mitochondria. Addition of 2 mM ADP after 5 μM CAT did not change the respiration, but increased the mitochondrial capacity for Ca 2+ at more than five times. Bongkrekic acid (BA) had a biphasic effect on PT. In the first minutes 5 μM BA increased the stability of mitochondrial membrane followed by a pronounced opening of PTP too. BA abolished the action about of 1 mM ADP, but was not able to induce swelling of mitochondria in the presence of 2 mM ADP. We conclude that the outer side of inner mitochondrial membrane has a low affinity sensor for ADP, modifying the activity of PTP. The pathophysiological importance of this process could be an endogenous prevention of PT at conditions of energetic depression. © 2004 Elsevier B.V. All rights reserved.

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Gizatullina, Z. Z., Chen, Y., Zierz, S., & Gellerich, F. N. (2005). Effects of extramitochondrial ADP on permeability transition of mouse liver mitochondria. Biochimica et Biophysica Acta - Bioenergetics, 1706(1–2), 98–104. https://doi.org/10.1016/j.bbabio.2004.09.013

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