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

FEBS Letters

Bohnensack, Ralf¹  Schönfeld, Peter¹ 

[1] Institute of Biochemistry, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany

关键词: Fatty acid;    Permeability transition;    Liver mitochondrion;    ADP/ATP carrier;    FFA;    non-esterified long-chain fatty acids;    AAC;    ADP/ATP carrier;    [3H]ATR;    atractyloside;    Phyt;    phytanic acid;    FCCP;    p-trifluoromethoxycarbonyl-cyanide phenylhydrazone;    MPT50%;    time of half-maximal swelling of mitochondrial fraction;   

DOI  :  10.1016/S0014-5793(97)01511-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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 (Δψ) 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 Δψ changes. In addition, FFA interact like their thioester derivatives in a structure-dependent manner with the ADP/ATP carrier (measured as inhibition of [³H]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.

【 授权许可】

Unknown