Related Experiment Videos
Apoptosis driven by IP(3)-linked mitochondrial calcium signals
G Szalai1, R Krishnamurthy, G Hajnóczky
1Department of Pathology, Anatomy and Cell Biology, Room 253 JAH, Thomas Jefferson University, Philadelphia, PA 19107, USA.
The EMBO Journal
|November 24, 1999
Summary
Apoptotic stimuli alter mitochondrial calcium signaling, triggering the permeability transition pore (PTP) opening and cytochrome c release. This process supports energy needs during cell death.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Mitochondrial calcium ([Ca(2+)](m)) regulates cellular energy metabolism.
- Calcium mobilizing agonists control cellular energy metabolism via [Ca(2+)](m).
Purpose of the Study:
- To investigate the role of mitochondrial calcium signaling in apoptosis.
- To understand the mechanism of permeability transition pore (PTP) opening during apoptosis.
Main Methods:
- Studied mitochondrial calcium signaling in response to apoptotic stimuli.
- Investigated the role of inositol trisphosphate (IP(3))-mediated calcium spikes.
- Analyzed cytochrome c release and PTP opening.
Main Results:
- Apoptotic stimuli switch mitochondrial calcium signaling, facilitating PTP opening.
- Both large calcium pulses and IP(3)-mediated calcium spikes trigger PTP opening and cytochrome c release.
- Mitochondrial metabolism recovers after PTP resealing, while caspases are activated by released cytochrome c.
Conclusions:
- A novel mechanism links mitochondrial calcium signaling to apoptosis.
- The cell maintains energy production during apoptosis through PTP dynamics.
- This coordinated process ensures efficient caspase activation and ATP supply for cell death.