This week we celebrate Mitochondrial Awareness Week, a dedicated time to turn our attention to these tiny yet incredibly powerful cellular structures that play a pivotal role in our health and well-being. While the mention of mitochondria might not immediately conjure up images of groundbreaking scientific discoveries, these dynamic organelles deserve a moment in the spotlight. They are the unsung heroes of our cells, and their importance extends far beyond just being the "powerhouses" that produce cellular energy.
In addition to being cellular “powerhouses” and generating the majority of a cells energy in the form of adenosine triphosphate (ATP), mitochondria are also involvement in apoptosis, calcium signalling, regulation of cellular metabolism and proliferation of haem and steroids.
Unfortunately, mitochondria are also a common target for drug-induced toxicity which can have a significant adverse effect on cellular function and overall health. Here are some key reasons why understanding the potential for mitochondrial toxicity is crucial when screening for a drug candidate:
- Energy Production: Any disruption in mitochondrial function can lead to a decrease in ATP production, which can have detrimental effects on cellular processes and overall cellular health.
- Cellular Health: Healthy mitochondria are essential for the proper functioning of cells and tissues. Mitochondrial dysfunction can lead to a range of health issues, including neurodegenerative diseases, cardiovascular diseases, and metabolic disorders.
- Potential Adverse Effects: Drugs that cause mitochondrial toxicity can lead to serious adverse effects in patients. For example, some drugs have been associated with muscle weakness, neuropathy, or liver damage due to their impact on mitochondria. Identifying mitochondrial toxicity during drug screening can help prevent these adverse effects in clinical trials and post-market use.
- Mitochondrial DNA Damage: Mitochondria have their own DNA (mtDNA), and they replicate independently of the cell nucleus. Drug-induced mitochondrial toxicity can result in mtDNA damage, mutations, or deletions. This can further impair mitochondrial function and contribute to a variety of diseases.
- Drug Efficacy: In addition to avoiding harm to mitochondria, it's important to consider the potential benefits of a drug on mitochondrial function. Some drug candidates may enhance mitochondrial function, which can be beneficial for diseases characterized by mitochondrial dysfunction, such as certain neurodegenerative disorders.
- Predictive Toxicology: Early identification of mitochondrial toxicity can help pharmaceutical companies make informed decisions about whether to advance a drug candidate in the development pipeline. Identifying mitochondrial toxicity in the preclinical stages allows for the modification of compounds or the discontinuation of those with high toxicity, potentially saving time and resources.
- Regulatory Requirements: Regulatory agencies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), require thorough safety assessments, including an evaluation of mitochondrial toxicity, during the drug development process. Failing to address mitochondrial toxicity issues can result in regulatory delays or rejection of a drug candidate.
In summary, studying mitochondrial toxicity is essential to ensure the safety and efficacy of drug candidates. It helps prevent potential harm to patients, reduces the risk of adverse effects, and supports the development of drugs that are not only effective but also safe for long-term use.
Cyprotex offer a number of approaches to study mitochondrial toxicity, including:
- Functional Mitochondrial Toxicity Assay (Seahorse)
- Mitochondrial Respiratory Complex Assay using Permeabilised Cells (Seahorse)
- Mitochondrial Biogenesis Assay
- Mitochondrial Glu/Gal Assay
- HCS Mitochondrial Toxicity Assay
In addition, we frequently publish our work in the field of understanding mitochondrial toxicity. You may be interested in:
Publication: A Combined In Vitro Approach to Improve the Prediction of Mitochondrial Toxicants
Contact us to find out more about our mitochondrial toxicity services today!
