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

Liang Guo, Dawn Pietkiewicz, Evgeny Pavlov, Sergey M. Grigoriev, John J. Kasianowicz, Laurent M. Dejean, Stanley J. Korsmeyer, Bruno Antonsson, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume286
Issue number5 55-5
DOIs
StatePublished - May 2004

Fingerprint

Cytochromes c
Apoptosis
Dextrans
Membranes
Pancreatic Ribonuclease
Mitochondria
Mitochondrial Membranes
Electric potential
Pore size
Noise
Salts

Keywords

  • Ion channels
  • Patch clamp

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Guo, L., Pietkiewicz, D., Pavlov, E., Grigoriev, S. M., Kasianowicz, J. J., Dejean, L. M., ... Kinnally, K. W. (2004). Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC. American Journal of Physiology - Cell Physiology, 286(5 55-5). https://doi.org/10.1152/ajpcell.00183.2003

Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC. / Guo, Liang; Pietkiewicz, Dawn; Pavlov, Evgeny; Grigoriev, Sergey M.; Kasianowicz, John J.; Dejean, Laurent M.; Korsmeyer, Stanley J.; Antonsson, Bruno; Kinnally, Kathleen W.

In: American Journal of Physiology - Cell Physiology, Vol. 286, No. 5 55-5, 05.2004.

Research output: Contribution to journalArticle

Guo, L, Pietkiewicz, D, Pavlov, E, Grigoriev, SM, Kasianowicz, JJ, Dejean, LM, Korsmeyer, SJ, Antonsson, B & Kinnally, KW 2004, 'Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC', American Journal of Physiology - Cell Physiology, vol. 286, no. 5 55-5. https://doi.org/10.1152/ajpcell.00183.2003
Guo, Liang ; Pietkiewicz, Dawn ; Pavlov, Evgeny ; Grigoriev, Sergey M. ; Kasianowicz, John J. ; Dejean, Laurent M. ; Korsmeyer, Stanley J. ; Antonsson, Bruno ; Kinnally, Kathleen W. / Effects of cytochrome c on the mitochondrial apoptosis-induced channel MAC. In: American Journal of Physiology - Cell Physiology. 2004 ; Vol. 286, No. 5 55-5.
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