Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC

Recent studies indicate that cytochrome c is released early in apoptosis without loss of integrity of the mitochondrial outer membrane in some cell types. The high-conductance mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane early in apoptosis of FL5.12 cells. Physiological...

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Published inAmerican Journal of Physiology: Cell Physiology Vol. 55; no. 5; pp. C1109 - C1117
Main Authors LIANG GUO, PIETKIEWICZ, Dawn, PAVLOV, Evgeny V, GRIGORIEV, Sergey M, KASIANOWICZ, John J, DEJEAN, Laurent M, KORSMEYER, Stanley J, ANTONSSON, Bruno, KINNALLY, Kathleen W
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Physiological Society 01.05.2004
Subjects
Ageing, cell death
Biological and medical sciences
Cell physiology
Cellular biology
Cytoskeleton
Fundamental and applied biological sciences. Psychology
Membranes
Molecular and cellular biology
Salt
Cytochrome c
Mitochondria
patch clamp
Cell death
Membrane transport
Membrane pore
ion channels
Apoptosis
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Summary:Recent studies indicate that cytochrome c is released early in apoptosis without loss of integrity of the mitochondrial outer membrane in some cell types. The high-conductance mitochondrial apoptosis-induced channel (MAC) forms in the outer membrane early in apoptosis of FL5.12 cells. Physiological (micromolar) levels of cytochrome c alter MAC activity, and these effects are referred to as types 1 and 2. Type 1 effects are consistent with a partitioning of cytochrome c into the pore of MAC and include a modest decrease in conductance that is dose and voltage dependent, reversible, and has an increase in noise. Type 2 effects may correspond to "plugging" of the pore or destabilization of the open state. Type 2 effects are a dose-dependent, voltage-independent, and irreversible decrease in conductance. MAC is a heterogeneous channel with variable conductance. Cytochrome c affects MAC in a pore size-dependent manner, with maximal effects of cytochrome c on MAC with conductance of 1.9-5.4 nS. The effects of cytochrome c, RNase A, and high salt on MAC indicate that size, rather than charge, is crucial. The effects of dextran molecules of various sizes indicate that the pore diameter of MAC is slightly larger than that of 17-kDa dextran, which should be sufficient to allow the passage of 12-kDa cytochrome c. These findings are consistent with the notion that MAC is the pore through which cytochrome c is released from mitochondria during apoptosis. [PUBLICATION ABSTRACT]
ISSN:0363-6143
1522-1563