The Dynamics of the Formation of Cytochrome c Complexes with Anionic Lipids and the Mechanism of the Production of Lipid Radicals Catalyzed by These Complexes. / Vladimirov, G. K.; Nesterova, A. M.; Levkina, A. A.; Osipov, A. N.; Teselkin, Y. O.; Kovalchuk, M. V.; Vladimirov, Yu A.
In: Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology, Vol. 14, No. 3, 01.07.2020, p. 232-241.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - The Dynamics of the Formation of Cytochrome c Complexes with Anionic Lipids and the Mechanism of the Production of Lipid Radicals Catalyzed by These Complexes
AU - Vladimirov, G. K.
AU - Nesterova, A. M.
AU - Levkina, A. A.
AU - Osipov, A. N.
AU - Teselkin, Y. O.
AU - Kovalchuk, M. V.
AU - Vladimirov, Yu A.
N1 - Publisher Copyright: © 2020, Pleiades Publishing, Ltd.
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Abstract: In the present work, the recorded kinetics of chemiluminescence enhanced by coumarin 334 indicated that the complexes of cytochrome c (Cyt) with anionic lipids (Cyt-AL), such as cardiolipin (CL) and phosphatidic acid (PA), when added to mitochondrial and cytoplasmic membranes, are capable of catalysing reactions of lipid free radical formation. The effect of Cyt-CL complex was studied on mitochondria isolated from the liver of male Wistar rats and male outbred mice, as well as on erythrocytes isolated from the blood of male Wistar rats. It was shown that complex Cyt-PA exerts a peroxidase effect similar to the effect produced by Cyt-CL. Upon exposure to Cyt-CL, the formation of free radicals was more prominent in mitochondrial ghosts (mitochondria subjected to freeze-thawing and washed by several precipitation–resuspension cycles) than in intact mitochondria. This suggests that Cyt-CL does not pass through biological membranes: even if it penetrates into them, it probably gets stuck in the phospholipid bilayer. Thus, the previously discovered cytotoxic effect of Cyt-CL on cancer cells is most likely due to peroxidation of the cytoplasmic membrane, but not of the inner membrane of mitochondria.
AB - Abstract: In the present work, the recorded kinetics of chemiluminescence enhanced by coumarin 334 indicated that the complexes of cytochrome c (Cyt) with anionic lipids (Cyt-AL), such as cardiolipin (CL) and phosphatidic acid (PA), when added to mitochondrial and cytoplasmic membranes, are capable of catalysing reactions of lipid free radical formation. The effect of Cyt-CL complex was studied on mitochondria isolated from the liver of male Wistar rats and male outbred mice, as well as on erythrocytes isolated from the blood of male Wistar rats. It was shown that complex Cyt-PA exerts a peroxidase effect similar to the effect produced by Cyt-CL. Upon exposure to Cyt-CL, the formation of free radicals was more prominent in mitochondrial ghosts (mitochondria subjected to freeze-thawing and washed by several precipitation–resuspension cycles) than in intact mitochondria. This suggests that Cyt-CL does not pass through biological membranes: even if it penetrates into them, it probably gets stuck in the phospholipid bilayer. Thus, the previously discovered cytotoxic effect of Cyt-CL on cancer cells is most likely due to peroxidation of the cytoplasmic membrane, but not of the inner membrane of mitochondria.
KW - apoptosis
KW - cardiolipin
KW - complex of cytochrome c with anionic lipids
KW - cytochrome c
KW - lipid peroxidation
KW - phosphatidic acid
UR - http://www.scopus.com/inward/record.url?scp=85092582628&partnerID=8YFLogxK
U2 - 10.1134/S1990747820030137
DO - 10.1134/S1990747820030137
M3 - Article
AN - SCOPUS:85092582628
VL - 14
SP - 232
EP - 241
JO - Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
JF - Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
SN - 1990-7478
IS - 3
ER -
ID: 88197815