TY - JOUR
T1 - Oxidative stress underlies the mechanism for Ca2+-induced permeability transition of mitochondria
AU - Kanno, Tomoko
AU - Sato, Eisuke F.
AU - Muranaka, Shikibu
AU - Fujita, Hirofumi
AU - Fujiwara, Takuzo
AU - Utsumi, Toshihiko
AU - Inoue, Masayasu
AU - Utsumi, Kozo
N1 - Funding Information:
This work was supported, in part, by grants from the Ministry of Education, Science and Literature, and the Japan Keirin Association.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/1
Y1 - 2004/1
N2 - Recent studies demonstrated that the generation of intracellular reactive oxygen species (ROS) was enhanced prior to the onset of mitochondrial membrane permeability transition (MPT), a critical step for the induction of DNA fragmentation and apoptosis. Although Ca2+ induces typical MPT that involves depolarization and swelling of mitochondria and finally releases cytochrome c into cytosol, the mechanism by which ROS induce MPT remains unclear. In the presence of inorganic phosphate, Ca2+ increased the oxygen consumption and ROS production by isolated mitochondria as determined by a chemiluminescence (CHL) method using L-012. Ca2+ increased the generation of H2O2 by some mechanism that was inhibited by cyclosporin A but not by superoxide dismutase (SOD) and trifluoperazine. Ca2+ decreased the content of free thiols in adenine nucleotide translocase (ANT) in mitochondrial membranes with concomitant increase in ROS generation. The presence of cyclosporin A, trifluoperazine, or SOD inhibited the Ca2+-induced increase of L-012 CHL and decrease in the free thiols of ANT. These results indicate that Ca2+ increases the generation of ROS which oxidize the free thiol groups in mitochondrial ANT, thereby inducing MPT to release cytochrome c.
AB - Recent studies demonstrated that the generation of intracellular reactive oxygen species (ROS) was enhanced prior to the onset of mitochondrial membrane permeability transition (MPT), a critical step for the induction of DNA fragmentation and apoptosis. Although Ca2+ induces typical MPT that involves depolarization and swelling of mitochondria and finally releases cytochrome c into cytosol, the mechanism by which ROS induce MPT remains unclear. In the presence of inorganic phosphate, Ca2+ increased the oxygen consumption and ROS production by isolated mitochondria as determined by a chemiluminescence (CHL) method using L-012. Ca2+ increased the generation of H2O2 by some mechanism that was inhibited by cyclosporin A but not by superoxide dismutase (SOD) and trifluoperazine. Ca2+ decreased the content of free thiols in adenine nucleotide translocase (ANT) in mitochondrial membranes with concomitant increase in ROS generation. The presence of cyclosporin A, trifluoperazine, or SOD inhibited the Ca2+-induced increase of L-012 CHL and decrease in the free thiols of ANT. These results indicate that Ca2+ increases the generation of ROS which oxidize the free thiol groups in mitochondrial ANT, thereby inducing MPT to release cytochrome c.
KW - Adenine nucleotide translocase
KW - Apoptosis
KW - Cyclosporin A
KW - Membrane permeability transition
KW - Protein thiol
KW - Reactive oxygen species
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U2 - 10.1080/10715760310001626266
DO - 10.1080/10715760310001626266
M3 - Review article
C2 - 15061651
AN - SCOPUS:1642464737
VL - 38
SP - 27
EP - 35
JO - Free Radical Research
JF - Free Radical Research
SN - 1071-5762
IS - 1
ER -