TY - JOUR
T1 - Channels in mitochondrial membranes
T2 - Knowns, unknowns, and prospects for the future
AU - Catia Sorgato, M.
AU - Moran, Oscar
AU - Pedersen, Peter L.
N1 - Funding Information:
The work carried out in the authors’ laboratories was funded in part by grants of the Con-siglio Nazionale delle Ricerche and of the Min-istero dell’ Universit6 e della Ricerca Scientifica e Tecnologica of Italy. The authors thank all those colleagues available to open discussions and those who critically read the manuscript. In particular, graditude is expressed to Dr. Cristina Ballarin for invaluable support throughout the preparation of the manuscript. This article is dedicated to the memory of Dr. Peter Mitchell, whose humanity and scholarly inventiveness will remain with many of us.
PY - 1993
Y1 - 1993
N2 - Rapid diffusion of hydrophilic molecules across the outer membrane of mitochondria has been related to the presence of a protein of 29 to 37 kDa, called voltage-dependent anion channel (VDAC), able to generate large aqueous pores when integrated in planar lipid bilayers. Functional properties of VDAC from different origins appear highly conserved in artificial membranes: at low transmembrane potentials, the channel is in a highly conducting state, but a raise of the potential (both positive and negative) reduces drastically the current and changes the ionic selectivity from slightly anionic to cationic. It has thus been suggested that VDAC is not a mere molecular sieve but that it may control mitochondrial physiology by restricting the access of metabolites of different valence in response to voltage and/or by interacting with a soluble protein of the intermembrane space. The latest application of the patch clamp and tip-dip techniques, however, has indicated both a different electric behavior of the outer membrane and that other proteins may play a role in the permeation of molecules. Biochemical studies, use of site-directed mutants, and electron microscopy of two-dimensional crystal arrays of VDAC have contributed to propose a monomelic β barrel as the structural model of the channel. An important insight into the physiology of the inner membrane of mammalian mitochondria has come from the direct observation of the membrane with the patch clamp. A slightly anionic., voltage-dependent conductance of 107 pS and one of 9.7 pS, K+-selective and ATP-sensitive, are the best characterized at the single channel level. Under certain conditions, however, the inner membrane can also show unselective nS peak transitions, possibly arising from a cooperative assembly of multiple substates.
AB - Rapid diffusion of hydrophilic molecules across the outer membrane of mitochondria has been related to the presence of a protein of 29 to 37 kDa, called voltage-dependent anion channel (VDAC), able to generate large aqueous pores when integrated in planar lipid bilayers. Functional properties of VDAC from different origins appear highly conserved in artificial membranes: at low transmembrane potentials, the channel is in a highly conducting state, but a raise of the potential (both positive and negative) reduces drastically the current and changes the ionic selectivity from slightly anionic to cationic. It has thus been suggested that VDAC is not a mere molecular sieve but that it may control mitochondrial physiology by restricting the access of metabolites of different valence in response to voltage and/or by interacting with a soluble protein of the intermembrane space. The latest application of the patch clamp and tip-dip techniques, however, has indicated both a different electric behavior of the outer membrane and that other proteins may play a role in the permeation of molecules. Biochemical studies, use of site-directed mutants, and electron microscopy of two-dimensional crystal arrays of VDAC have contributed to propose a monomelic β barrel as the structural model of the channel. An important insight into the physiology of the inner membrane of mammalian mitochondria has come from the direct observation of the membrane with the patch clamp. A slightly anionic., voltage-dependent conductance of 107 pS and one of 9.7 pS, K+-selective and ATP-sensitive, are the best characterized at the single channel level. Under certain conditions, however, the inner membrane can also show unselective nS peak transitions, possibly arising from a cooperative assembly of multiple substates.
KW - Inner membrane channels
KW - MCS channel
KW - Mitochondria
KW - Outer membrane channels
KW - Patch clamp
KW - Planar lipid bilayer
KW - VDAC
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U2 - 10.3109/10409239309086793
DO - 10.3109/10409239309086793
M3 - Article
C2 - 7683593
AN - SCOPUS:0027238514
SN - 1040-9238
VL - 28
SP - 127
EP - 171
JO - Critical reviews in biochemistry and molecular biology
JF - Critical reviews in biochemistry and molecular biology
IS - 2
ER -