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Updated: Jun 20, 2026

Cellular Redox Profiling Using High-content Microscopy
Published on: May 14, 2017
MAC inhibitors suppress mitochondrial apoptosis
Pablo M Peixoto1, Shin-Young Ryu, Agnes Bombrun
1Department of Basic Sciences, New York University College of Dentistry, New York, NY 10010, USA.
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 this mitochondrial channel is a promising therapeutic target.
Insights
Compounds that close the mitochondrial apoptosis-induced channel (MAC) can prevent cell death. These compounds effectively blocked cytochrome c release and halted apoptosis, indicating MAC is a potential therapeutic target.
Area of Science:
- Cell Biology
- Biochemistry
- Pharmacology
Background:
- The mitochondrial apoptosis-induced channel (MAC) is crucial for intrinsic apoptosis, mediating cytochrome c release.
- MAC opening is a key commitment step in programmed cell death.
- Inhibiting MAC could represent a therapeutic strategy to prevent apoptosis.
Purpose of the Study:
- To identify and characterize compounds that can directly close MAC.
- To evaluate the efficacy of these compounds in suppressing apoptosis in cellular models.
Main Methods:
- Recombinant Bax protein was used to assess compound efficacy in blocking fluorescein release from liposomes.
- Compounds were tested for their ability to directly close MAC.
- Apoptosis was induced in FL5.12 cells via IL-3 deprivation or staurosporine treatment.
- Cytochrome c release and apoptotic markers were monitored.
Main Results:
- Several compounds were identified that irreversibly closed MAC at low concentrations (IC50: 19–966 nM).
- These compounds effectively inhibited cytochrome c release.
- The tested compounds suppressed the onset of apoptotic markers induced by IL-3 deprivation or staurosporine.
Conclusions:
- A direct link exists between MAC activity, cytochrome c release, and apoptotic cell death.
- The mitochondrial apoptosis-induced channel (MAC) is a viable therapeutic target for preventing apoptosis.
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