Titration of cardiolipin by either 10-N-nonyl acridine orange or acridine orange sensitizes the adenine nucleotide carrier to permeability transition.
Under the action of carboxyatractyloside or fatty acids, adenine nucleotide translocase switches its function from nucleotide carrier to modulator of the opening of a non-specific pore. In addition to the effect of these agents, this modification in activity is, in some way, dependent on the influence of the lipid milieu of the membrane. Cardiolipin is, among other membrane phospholipids, the one that interacts the most with the translocase. This work shows that 10-N-nonyl acridine orange and acridine orange, probes for this phospholipid, modify the sensitivity of the translocase to carboxyatractyloside, oleate, and palmitate to induce permeability transition. The results also show that these probes stimulate the release of mitochondrial cytochrome c, and increase labeling of the carrier by eosin 5-maleimide. Based on the aforementioned it is proposed that the increase in sensitivity is due to a conformational change in the translocase, induced by the binding of the probe to cardiolipin.
Chávez
Edmundo
E
Departamento de Bioquímica, Instituto Nacional de Cardiología, Ignacio Chávez, Juan Badiano No. 1, Col. Sección XVI, Tlalpan, 014080, Mexico City, Mexico. echavez@salud.gob.mx
Zazueta
Cecilia
C
García
Noemí
N
Martínez-Abundis
Eduardo
E
Pavón
Natalia
N
Hernández-Esquivel
Luz
L
D000165:Acridine Orange / Q000737:chemistry*; D000818:Animals; D002308:Cardiolipins / Q000737:chemistry* / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017186:Titrimetry
D002308:Cardiolipins; D000226:Mitochondrial ADP, ATP Translocases; D000165:Acridine Orange