For a detailed guide to mitochondrial toxicity, please review our Application Guide.

This guide provides useful information about the assays that can be used, with example data provided, along with information about crucial subjects to consider such as cell type(s) to use, and growth and dosing conditions.

Consulting Services

For those conducting screening projects or investigational studies of mitochondrial toxicity or up-regulation of mitochondrial function who would like assistance in designing studies and interpreting data, MitoSciences can provide consultation services in these areas. Drawing on the complete range of tools available for evaluating cellular bioenergetics, mitochondrial function, and mitochondrial proteomics, MitoSciences can help in the design of the most efficient studies and interpretation of results against known data sets for control/comparison compounds. Assays available to the researcher can generally be categorized as either Screening Assays or Investigational Assays.

The set of Screening Assays includes several which are commonly utilized in HCS systems:
1. ATP Production
2. Oxygen Consumption
3. Mitochondrial Membrane Potential
4. ROS Production
5. Total Glutatione Level
6. Caspase 3 Activation
7. PARP Activation

Between these assays are covered measurements of disruption of energy metabolism, increased oxidative stress, and induction of apoptosis, which are the three general toxic effects that drugs can have on mitochondria. All of these assays can be performed in high-throughput, and all can be performed in multiple cell types.

Investigational Assays are typically utilized as a follow-up to either animal experiments or high-content screening after one or both have suggested mitochondrial toxicity. The assays performed during Investigational Studies seek to provide detailed information on the mechanism-of-action for any identified toxic effect. These data can then be used as biomarkers in further animal studies or clinical trials, to guide compound redesign, or used during in vitro screening of future compounds.

Investigational Assays include:
1. Metabolic Enzyme Activity
2. Metabolic Protein Expression
3. Metabolic Protein Post-Translational Modifications (phosphorylation, acetylation)
4. Protein-Specific Oxidative/Nitrative Modification
5. Apoptosis Protein Translocation

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