Mitochondria: what you need to know

What is the mithochondrion?

The mitochondrion, an essential organelle

The mitochondrion is a highly interacting organnelle at the center of cell vitality and function. Mitochondria have several essential roles within the cell and are involved in many important mechanisms.

The mitochondrion, subject of exploration

There is still much to learn about mitochondria and their participation in cellular activity, as well as their involvement in different diseases, including CNS diseases, cancer and metabolic diseases, and in drug-induced toxicity. Our knowledge and understanding of mitochondrial and cellular interactions is constantly improving.

Targeting mitochondria

Potential disease applications

Mitochondria are essential to cell metabolism and survival. Their molecular constituents are key targets of drug development in metabolic disease, cancer, CNS diseases and cardiovascular risk management. In these different diseases, altered mitochondrial function and behaviour have been recognized. In cancer cells for instance, the Warburg effect, which is a shift from oxydative phosphorylation to glycolysis, even in the presence of oxygen, can be observed. Indeed, different cancer cell lines have different Warburg statuses and different central metabolism markers, and respond differently to anti-cancer drugs.

What impact can you have?

The mitochondria: a novel target for drug development
You can target mitochondria to try to reverse the effects a specific disease might have on them, or to trigger the apoptosis in diseased cells. While mitochondrial targeting presents many challenges, such as delivery, it also presents many opportunities in drug development. Targeting mitochondrial bioenergetics with uncouplers is explored by anti-cancer drugs and anti-obesity drugs. Targeting apoptosis through the permeability transition pore has been validated in cancer and in cardio-protection. Equilibrating Redox-status is targeted in hypoxic conditions, CNS defects and in infectious diseases…

Targets for toxicity

Drugs, whatever their targets, can also injure mitochondria since off-target effects of drugs may impact the mitochondrial electron transfer chain, mitochondrial DNA content and balance in the REDOX status of the cell. Mitochondrial dysfunction has been recognized as one of the most important causes of drug-induced liver and cardiac injuries. As such, mitochondria are a very pertinent target for toxicity.

Why and when should you care?

What can you learn from mitochondria?

Mitochondria play a central role in cells and are affected in many diseases. Understanding a disease’s impact on mitochondria is going one step closer to understanding the disease. Studying the mitochondria can also help you move more swiftly along the lengthy process of drug development and approval by detecting efficacy and toxicity. Early screening in the pre-clinical stage can make you save time and money, by ensuring that you are pursuing the best and the safest drug.

Determine the right patients for your drugs

Drugs can have different effects on a given population. mtBiolabs develops decision-making technologies to help its partners develop safer and more targeted drugs.

Indeed, mitochondria can also help you to determine the specific profiles of those cell-lines that are most responsive to your drug, or which react adversely to it, in order to ultimately target the appropriate patients.

mtBiolabs combines system biology and molecular exploration to achieve separation of homogeneous phenotype-groups inside a population, leading to the unique discovery of pertinent biomarkers. Metabolic profiles can lead to a companion diagnostic tool to ensure your drug reaches those who are most responsive to it and will thus benefit most from it.

mtBiolabs helps pave your way toward more accurate personalized medicine.

Screen for efficacy

Many diseases impact mitochondrial function and behavior, or concern mitochondrial metabolic pathways. Examining molecules’ ability to reverse these alterations at an early stage can help you select the most effective drug to push forward. Establishing efficacy at this stage, in patient-derived cell models, also contributes to proving your drug’s value, facilitating adhesion of investors or inductrial partners to your critical path.

Screen for toxicity

Different mitochondrial impairements have been associated to liver and cardio toxicity1, due to drugs or metabolites. Screening mitochondria for toxicity maximizes your chances of reaching a profitable market by greatly reducing the risks of unsuspected adverse effects appearing late in development or once on market.

1. Jatoe et al. drug metabol, drug interaction 1988; Lores and Llesus, Toxicol, 1993, review in Menna et al., Chem Res Tox, 2010; Masubuchi et al. Biochem pharmacol, 1999; Brunmair et al., J parmacol exp, 2004; Dykens & Will, DDT, 2007.