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Fatty acid‐promoted mitochondrial permeability transition by membrane depolarization and binding to the ADP/ATP carrier
Author(s) -
Schönfeld Peter,
Bohnensack Ralf
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)01511-1
Subject(s) - mitochondrial permeability transition pore , chemistry , biophysics , mitochondrion , membrane potential , depolarization , inner mitochondrial membrane , biochemistry , cytosol , permeability (electromagnetism) , fatty acid , transmembrane protein , chemiosmosis , membrane , atp synthase , enzyme , biology , receptor , apoptosis , programmed cell death
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 [ 3 H]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.