Fatty acid-promoted mitochondrial permeability transition by membrane depolarization and binding to the ADP/ATP carrier

被引:100
作者
Schönfeld, P [1 ]
Bohnensack, R [1 ]
机构
[1] Otto Von Guericke Univ, Inst Biochem, D-39120 Magdeburg, Germany
来源
FEBS LETTERS | 1997年 / 420卷 / 2-3期
关键词
fatty acid; permeability transition; liver mitochondrion; ADP/ATP carrier;
D O I
10.1016/S0014-5793(97)01511-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The mechanism by which non-esterified long-chain fatty acids (FFA) promote mitochondrial permeability transition (MPT) is not clear, We examined with energized rat liver mitochondria the role of two possible actions of FFA in MPT, (i) the reduction of the transmembrane potential (Delta psi) and (ii) the increase of the negative surface charge of the inner mitochondrial membrane [Broekemeier, K.M. and Pfeiffer, D.G., Biochemistry 43, (1995) 16440-16449], It was found that the ability of FFA to stimulate large amplitude swelling is clearly related to their uncoupling activity, Moreover, compared with classical protonophores (FCCP) FFA increase the sensitivity of the pore opening process to Delta psi changes, In addition, FFA interact like their thioester derivatives in a structure-dependent manner with the ADP/ATP carrier (measured as inhibition of [H-3]atractyloside binding to the AAC protein), It is suggested that not only the protonophoric action of FFA, but also a presumable stabilization of the 'cytosolic' conformation of AAC contribute to the FFA-promoted MPT. (C) 1997 Federation of European Biochemical Societies.
引用
收藏
页码:167 / 170
页数:4
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