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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Cardioprotective signaling to mitochondria
Keith D Garlid1, Alexandre D T Costa, Casey L Quinlan
1Department of Biology, Portland State University, Portland, OR 97201-0751, USA. garlid@pdx.edu
Journal of Molecular and Cellular Cardiology
|January 3, 2009
Summary
Mitochondria protect the heart during ischemia-reperfusion injury. Signaling molecules form signalosomes that activate mitochondrial pathways, opening the mitochondrial ATP-sensitive K(+) channel (mitoK(ATP)) to reduce cell death.
Area of Science:
- Cardiovascular Physiology
- Mitochondrial Biology
- Cell Signaling
Background:
- Mitochondria play a critical role in ischemia-reperfusion (I/R) injury.
- Activation of plasma membrane receptors or Na,K-ATPase initiates cardioprotective signaling.
- Understanding these pathways is crucial for developing treatments for heart damage.
Purpose of the Study:
- To review experimental findings supporting the hypothesis that signalosomes mediate cardioprotection during I/R.
- To elucidate the role of receptor migration to caveolae and signalosome formation.
- To detail the intramitochondrial signaling cascade initiated by signalosome-mitochondria interaction.
Main Methods:
- Review of existing experimental data on I/R pathophysiology.
- Analysis of signaling pathways involving G-coupled receptors and Na,K-ATPase.
- Examination of signalosome formation, trafficking, and interaction with mitochondria.
- Investigation of mitochondrial signaling, including mitoK(ATP) channel opening, ROS production, and PKCε activation.
Main Results:
- Receptor activation leads to signalosome formation in caveolae.
- Signalosomes migrate to mitochondria, initiating intramitochondrial signaling.
- MitoK(ATP) channel opening increases ROS production.
- PKCε activation inhibits the mitochondrial permeability transition (MPT), reducing cell death.
Conclusions:
- Signalosome-mitochondria interaction is a key mechanism of cardioprotection in I/R.
- Activation of mitoK(ATP) by signalosomes triggers a protective cascade.
- This pathway effectively reduces cell death during I/R events.
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