Cardioprotection

Literature highlights

The mitochondrion is a complex organelle that serves essential roles in energy transduction, ATP production, and a myriad of cellular signaling events. A finely tuned regulatory network orchestrates the biogenesis, maintenance, and turnover of mitochondria. The high-capacity mitochondrial system in the heart is regulated in a dynamic way to generate and consume enormous amounts of ATP in order to support the constant pumping function in the context of changing energy demands.1

To maintain constant ATP production, malfunctioning mitochondria are constantly replaced by newly synthetized organelles by processes involving mitochondrial biogenesis and replication and autophagy/mitophagy.2, 3 These processes work in a tightly regulated manner, with mitochondrial fusion and fission allowing the dynamic formation and remodeling of a reticulated mitochondrial network.4 Since mitochondria are responsible for the production of ATP, agents that interfere with the physiological myocardial mitochondrial function are expected to induce depletion of ATP pool. Eventually, these processes may lead to subsequent myocardial dysfunction.

1. Dorn G. W., Vega R. B., and Kelly D. P. Mitochondrial biogenesis and dynamics in the developing and diseased heart. Genes Dev. 2015 Oct 1; 29(19):1981-91.

2. Fischer F., Hamann A., and Osiewacz H. D. Mitochondrial quality control: an integrated network of pathways. Trends Biochem. Sci. 2012; 37: 284–292.

3. Varga Z. V., Giricz Z., Liaudet L., Hasko G., Ferdinandy P., and Pacher P. Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy. Biochim. Biophys. Acta. 2014; 1852: 232–242.

4. Archer S. L. Mitochondrial dynamics—mitochondrial fission and fusion in human diseases. N. Engl. J. Med. 2013; 369: 2236–2251.

All our assays are fully customizable and can be adapted to meet your specific needs. Contact us to learn how our technologies might be of value to you!

Which technologies to use

mtDNA content and quality control

Abnormal levels in mtDNA content is a hallmark of cardiomyopathies. Screen against this using our quantitative High Content Analysis (HCA) reading of mtDNA content.

This package consists of the multiplexed and integrated measurements, in a same cell, of:

  • Mitochondrial DNA content
  • Mitochondrial mass
  • Mitochondrial biogenesis
  • Cell viability
  • Nucleus integrity and morphology, an apoptotic marker (optional)

mtDNA quality control (mytophagy and fusion/fission dynamics) can also be assessed upon request.

BBS or BBS + package

ICDD's Bioenergetic Balance Screen (BBS/BBS+) helps you get a finer understanding of your drug's mechanism of action at the mitochondrial level, and evaluate your compound's impact on β-oxidation, oxidative phosphorylation (OXPHOS) and the tricarboxylic (TCA) cycle.

Using the BBS, you can also assess the impact of your drug as a potential source of unwanted toxicity.

The BBS+ package is the multiplexed and integrated measurements, in a same cell, of:

  • Oxygen consumption
  • ATP production
  • Glycolysis level
  • Cell viability
  • TCA cycle turning (BBS+ only)

The BBS+ package is available in HTS/dose response studies.

Redox status

Our Redox status package, avalaible in HTS/dose response studies, is the measurement of (any or all):

  • ROS mitochondrial production
  • Cytoplasm ROS accumulation
  • MnSOD Cu/ZnSOD activities
  • Catalase activity
  • Total GSH activity
  • Lipid peroxidation level (TBARS)
  • Protein carbonylation
  • Cell viability