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Updated: Apr 22, 2026

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue

Published on: March 23, 2015

Profiling of the Tox21 chemical collection for mitochondrial function to identify compounds that acutely decrease

Matias S Attene-Ramos¹, Ruili Huang, Sam Michael

¹National Center for Advancing Translational Sciences, National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Bethesda, Maryland, USA.

Environmental Health Perspectives

|October 11, 2014

Summary

This summary is machine-generated.

Researchers screened thousands of chemicals to find those impacting mitochondrial membrane potential (MMP). This study identified specific compounds and structural features that decrease MMP, aiding in predicting chemical toxicity and disease links.

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Area of Science:

Toxicology
Mitochondrial Biology
Chemical Screening

Background:

Mitochondrial dysfunction is linked to diseases like cancer, diabetes, and neurodegeneration.
Environmental chemicals and drugs can impact mitochondrial function, influencing toxicity and disease onset.

Purpose of the Study:

Identify specific chemicals and structural features that alter mitochondrial membrane potential (MMP).
Predict chemical toxicity and potential roles in disease pathogenesis.

Main Methods:

Utilized a multiplexed quantitative high-throughput screening (qHTS) assay measuring MMP and adenosine triphosphate (ATP) content.
Screened the Tox21 library of ~8,300 unique chemicals at 15 concentrations in triplicate using HepG2 cells.
Employed informatics and structure-based clustering analysis.

Main Results:

Approximately 11% of compounds (913 unique) decreased MMP without affecting cell viability (ATP).
309 compounds decreased MMP at concentrations also causing cytotoxicity.
Over 11% of structural clusters were enriched for MMP-decreasing compounds.

Conclusions:

The multiplexed qHTS approach generated a reliable dataset for evaluating MMP-decreasing compounds.
Structure-based clustering identified molecular features responsible for observed MMP changes.