MAC inhibitors suppress mitochondrial apoptosis

Pablo M. Peixoto, Shin Young Ryu, Agnes Bombrun, Bruno Antonsson, Kathleen W. Kinnally

Research output: Contribution to journalArticle

Abstract

MAC (mitochondrial apoptosis-induced channel) forms in the mitochondrial outer membrane and unleashes cytochrome c to orchestrate the execution of the cell. MAC opening is the commitment step of intrinsic apoptosis. Hence closure of MAC may prevent apoptosis. Compounds that blocked the release of fluorescein from liposomes by recombinant Bax were tested for their ability to directly close MAC and suppress apoptosis in FL5.12 cells. Low doses of these compounds (IC50 values ranged from 19 to 966 nM) irreversibly closed MAC. These compounds also blocked cytochrome c release and halted the onset of apoptotic markers normally induced by IL-3 (interleukin-3) deprivation or staurosporine. Our results reveal the tight link among MAC activity, cytochrome c release and apoptotic death, and indicate thismitochondrial channel is a promising therapeutic target.

Original languageEnglish (US)
Pages (from-to)381-387
Number of pages7
JournalBiochemical Journal
Volume423
Issue number3
DOIs
StatePublished - Nov 1 2009

Fingerprint

Apoptosis
Cytochromes c
Staurosporine
Interleukin-3
Mitochondrial Membranes
Fluorescein
Liposomes
Inhibitory Concentration 50
Membranes

Keywords

  • Apoptosis
  • Cytochrome c release
  • Interleukin-3
  • Mitochondrial apoptosis-induced channel (MAC)
  • Patch-clamp
  • Staurosporine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Peixoto, P. M., Ryu, S. Y., Bombrun, A., Antonsson, B., & Kinnally, K. W. (2009). MAC inhibitors suppress mitochondrial apoptosis. Biochemical Journal, 423(3), 381-387. https://doi.org/10.1042/BJ20090664

MAC inhibitors suppress mitochondrial apoptosis. / Peixoto, Pablo M.; Ryu, Shin Young; Bombrun, Agnes; Antonsson, Bruno; Kinnally, Kathleen W.

In: Biochemical Journal, Vol. 423, No. 3, 01.11.2009, p. 381-387.

Research output: Contribution to journalArticle

Peixoto, PM, Ryu, SY, Bombrun, A, Antonsson, B & Kinnally, KW 2009, 'MAC inhibitors suppress mitochondrial apoptosis', Biochemical Journal, vol. 423, no. 3, pp. 381-387. https://doi.org/10.1042/BJ20090664
Peixoto PM, Ryu SY, Bombrun A, Antonsson B, Kinnally KW. MAC inhibitors suppress mitochondrial apoptosis. Biochemical Journal. 2009 Nov 1;423(3):381-387. https://doi.org/10.1042/BJ20090664
Peixoto, Pablo M. ; Ryu, Shin Young ; Bombrun, Agnes ; Antonsson, Bruno ; Kinnally, Kathleen W. / MAC inhibitors suppress mitochondrial apoptosis. In: Biochemical Journal. 2009 ; Vol. 423, No. 3. pp. 381-387.
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