Permeability transition-independent release of mitochondrial cytochrome c induced by valinomycin.
To examine whether valinomycin induces a mitochondrial permeability transition (PT), we investigated its effects on mitochondrial functions under various conditions. The acceleration of mitochondrial respiration and swelling, induced by valinomycin, were found to be insensitive to inhibitors of the ordinary PT, indicating that valinomycin does not induce the ordinary PT. Results of experiments using mitochondria isolated from transgenic mice expressing human bcl-2 also supported this conclusion. Furthermore, evidence for induction of PT pores by valinomycin was not obtained by either electron microscopic analysis of mitochondrial configurations or by measurement of the permeability of the inner mitochondrial membrane by use of polyethylene glycol. However, valinomycin did induce a significant release of cytochrome c, and thus it may be a nice tool to study the processes of mitochondrial cytochrome c release.
Shinohara
Yasuo
Y
Faculty of Pharmaceutical Sciences, University of Tokushima, Japan. yasuo@ph.tokushima-u.ac.jp
Almofti
Mohamad Radwan
MR
Yamamoto
Takenori
T
Ishida
Taro
T
Kita
Fumiyo
F
Kanzaki
Hideki
H
Ohnishi
Masakatsu
M
Yamashita
Kikuji
K
Shimizu
Shigeomi
S
Terada
Hiroshi
H
D000818:Animals; D001923:Brain Chemistry; D003574:Cytochrome c Group / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D010539:Permeability / Q000187:drug effects; D011092:Polyethylene Glycols / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014634:Valinomycin / Q000494:pharmacology*
D003574:Cytochrome c Group; D007476:Ionophores; D019253:Proto-Oncogene Proteins c-bcl-2; D014634:Valinomycin; D011092:Polyethylene Glycols